Krishnaswami Raja - Academia.edu (original) (raw)

Papers by Krishnaswami Raja

ChemInform, 2010

The Concept of a Green Drug: Curcumin and Its Derivatives as a Model System -[45 refs.]. -(RAJA, ... more The Concept of a Green Drug: Curcumin and Its Derivatives as a Model System -[45 refs.]. -(RAJA, K. S.; BALAMBIKA, R.; DOLAI, S.; SHI, W.; Mini-Rev. Org. Chem. 6 (2009) 2, 152-158; Dep. Chem., Coll. Staten Island, City Univ. New York, Staten Island, NY 10301, USA; Eng.) -Lindner 05-255

ACS chemical neuroscience, Jan 21, 2011

The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative of cu... more The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative of curcumin with amplified bioefficacy in modulating amyloid-β and tau peptide aggregation is presented. Curcumin inhibits amyloid-β and tau peptide aggregation at micromolar concentrations; the sugar-curcumin conjugate inhibits Aβ and tau peptide aggregation at concentrations as low as 8 nM and 0.1 nM, respectively. In comparison to curcumin, this conveniently synthesized Alzheimer's drug candidate is a more powerful antioxidant.

Organic Letters, 2007

Curcumin, the primary active ingredient in the spice turmeric, was converted to reactive monofunc... more Curcumin, the primary active ingredient in the spice turmeric, was converted to reactive monofunctional derivatives (carboxylic acid/azide/ alkyne). The derivatives were employed to produce a 3 + 2 azide−alkyne "clicked" curcumin dimer and a poly(amidoamine) (PAMAM) dendrimer− curcumin conjugate. The monofunctional curcumin derivatives retain biological activity and are efficient for labeling and dissolving amyloid fibrils. The curcumin dimer selectively destroys human neurotumor cells. The synthetic methodology developed affords a general strategy for attaching curcumin to various macromolecular scaffolds.

Mini-Reviews in Organic Chemistry, 2009

... I have closely interacted with a Siddha Physician (Dr. Paul Nadar) based ... FORMU-LATIONS, O... more ... I have closely interacted with a Siddha Physician (Dr. Paul Nadar) based ... FORMU-LATIONS, ORGANOMETALLIC COMPLEXES AND CUR-CUMIN DERIVATIVES Formulations Nanoparticles formed by ... Nanocurcumin particles were ~50 nm in size, bioefficacy of this construct ...

Microscopy and Microanalysis, 2008

Combinations of conjugated organic oligomers and inorganic quantum dots bring together the respec... more Combinations of conjugated organic oligomers and inorganic quantum dots bring together the respective valuable opto-electronic properties such as electroluminescence, photoconductivity, and photoluminescence [1-4] for the development of novel applications, e.g. nanoelectronics. Recent efforts in our laboratory lead to the network formation between biotin-functionalized oligo(pphenylene vinylene)s (OPVs) and streptavidin coated quantum dots (Qdots), Scheme 1. We wished to develop a comprehensive microscopic approach involving confocal fluorescence laser scanning microscopy (CFLSM) and transmission electron microscopy (TEM) to understand the formed aggregates structurally and functionally.

International Journal of Cancer, 2014

Current therapies for glioblastoma are largely palliative, involving surgical resection followed ... more Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-jB, P-Akt1, vascular endothelial growth factor, cyclin D1 and BCl XL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-jB conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-jB played a key role in protecting glioblastoma cells. To enhance delivery, we coupled curcumin to the glioblastoma-specific CD68 antibody in a releasable form. This resulted in a 120-fold increase in its efficacy to eliminate GL261 cells. A very similar dose response was also obtained with human glioblastoma lines T98G and U87MG. GL261-implanted mice receiving intratumor infusions of the curcumin-CD68 adduct followed by tail-vein injections of solubilized curcumin displayed a fourfold to fivefold reduction in brain tumor load, survived longer, and about 10% of them lived beyond 100 days. Hematoxylin-eosin staining of brain sections revealed a small scar tissue mass in the rescued mice, indicating adduct-mediated elimination of glioblastoma tumor. The tumor cells were strongly CD681 and some cells in the tumor periphery were strongly positive for microglial Iba1, but weakly positive for CD68. This strategy of antibody targeting of curcumin to tumor comes with the promise of yielding a highly effective therapy for glioblastoma brain tumors.

International Journal of Cancer, 2012

In vitro studies have shown that curcumin, a polyphenol from the culinary component turmeric, has... more In vitro studies have shown that curcumin, a polyphenol from the culinary component turmeric, has strong anticancer properties. However, there is no consensus on its therapeutic effect in human. Our earlier experiments involving implanted murine melanoma B16F10 cells in the neck or brain of syngeneic C57BL6 mice showed that tail vein injection of curcumin blocks formation of lesions and tumor in these mice. However, such treatment was ineffective in eliminating established tumors that already occupied 10% of brain volume. Possible reasons include low solubility and rapid metabolism of curcumin in vivo. To increase its efficacy, we have linked curcumin through a cleavable arm to an antibody (Ab) against the melanoma surface antigen Muc18. The antibody-coupled curcumin was 230-fold more effective in eliminating B16F10 cells in vitro, and in vivo, it rapidly decimated established, B16F10-evoked brain tumors, enabling the rescued mice to live normally far beyond 90 days from implantation of cancer cells. In contrast, mice treated with Muc18 Ab alone died of brain tumor within a month. In B16F10 cells, curcumin-Ab (adduct) treatment caused a dramatic inhibition of NF-kB: a transcription factor that is constitutively activated in cancer cells. Furthermore, overexpression of NF-kB in the B16F10 cells blocked adduct-evoked stimulation of caspase-3/7 activity. Thus, by suppressing NF-kB, the curcumin adduct inhibits other downstream tumor-promoting proteins, thereby eliminating the B16F10 cells. Our study submits a novel yet generally applicable strategy of converting curcumin into a potent anticancer agent and provides a mechanistic framework for its action.

Chemical Communications, 2005

The Cu(I)-catalyzed ATRP and azide-alkyne cycloaddition reactions together provide a versatile me... more The Cu(I)-catalyzed ATRP and azide-alkyne cycloaddition reactions together provide a versatile method for the synthesis of end-functionalized glycopolymers and their attachment to a suitably modified viral protein scaffold.

Biomacromolecules, 2003

Cowpea mosaic virus was derivatized with poly(ethylene glycol) to give well-controlled loadings o... more Cowpea mosaic virus was derivatized with poly(ethylene glycol) to give well-controlled loadings of polymer on the outer surface of the coat protein assembly. The resulting conjugates displayed altered densities and immunogenicities, consistent with the known chemical and biological properties of PEG. These studies make CPMV potentially useful as a tailored vehicle for drug delivery.

Bioconjugate Chemistry, 2009

Azide-terminated poly(tert-butyl acrylate) was synthesized via atom transfer radical polymerizati... more Azide-terminated poly(tert-butyl acrylate) was synthesized via atom transfer radical polymerization (ATRP). Subsequent deprotection was performed to yield poly(acrylic acid) (PAA) possessing a reactive chain-end. A one-pot sequential amidation of the PAA with the amine derivatives of a near-infrared fluorescent dye (ADS832WS) and glucose produced NIRF dye-incorporated water-soluble copolymers. End-group modifications were performed to produce alkyne/biotin-terminated copolymers which were further employed to generate dye-incorporated polymer-protein hybrids via the biotin-avidin interaction with avidin or "click" bioconjugation with azidemodified BSA. We have overcome two fundamental limitations in the synthesis of bioconjugates: (a) the basic restriction in the diversity of copolymers which can be synthesized for producing bioconjugates, (b) the limitation in the number of dyes/drug molecules that can be attached per protein molecule. The copolymers possessed enhanced optical properties compared to the dye due to increased solubility in water. Potential utility of these copolymers and conjugates in multiwell plate based assays, cell surface imaging and in vivo animal imaging were explored.

Bioconjugate Chemistry, 2003

Nonenveloped viruses provide the chemist with large, preassembled polyvalent protein scaffolds fo... more Nonenveloped viruses provide the chemist with large, preassembled polyvalent protein scaffolds for modification. These structures are typically porous to small molecules but not to large ones. The solution-phase structures and reactivities of such assemblies may be substantially different than indicated by X-ray crystal structures. Here, the attachment of organic compounds to either the inside or outside surface of the cowpea mosaic virus (CPMV) coat protein was verified with an indicating antibody-antigen interaction. Antibody binding was subsequently blocked by the installation of poly-(ethylene glycol) chains. These results typify the type of site-specific control that is available with CPMV and related virus building blocks.

Anti-Cancer Agents in Medicinal Chemistry, 2013

Curcumin, which is derived from the plant Curcuma longa, has received considerable attention as a... more Curcumin, which is derived from the plant Curcuma longa, has received considerable attention as a possible anti-cancer agent. In cell culture, curcumin is capable of inducing apoptosis in cancer cells at concentrations that do not affect normal cells. One draw-back holding curcumin back from being an effective anti-cancer agent in humans is that it is almost completely insoluble in water and therefore has poor absorption and subsequently poor bioavailability. Here we have generated a number of curcumin derivatives (tetrahydro-curcumin, curcumin mono-carboxylic acid, curcumin mono-galactose, curcumin mono-alkyne and dendrimer-curcumin conjugate) to test whether any of them display both cytotoxicity and water solubility. Of those tested only dendrimer-curcumin conjugate exhibited both water solubility and cytotoxicity against SKBr3 and BT549 breast cancer cells. When compared to curcumin dissolved in DMSO, dendrimer-curcumin conjugate dissolved in water was significantly more effective in inducing cytotoxicity, as measured by the MTT assay and effectively induced cellular apoptosis measured by caspase-3 activation. Since dendrimer-curcumin conjugate is water soluble and capable of inducing potent cytotoxic effects on breast cancer cell lines, it may prove to be an effective anti-cancer therapy to be used in humans.

Anti-Cancer Agents in Medicinal Chemistry, 2013

The concept of Ayurvedic expert guided drug discovery and development is defined and put to test ... more The concept of Ayurvedic expert guided drug discovery and development is defined and put to test systematically for the first time in literature. Western Science has explored only ~5% of the approximately 25,000 species of higher plants for drug leads. The ancient medical science of Ayurveda has however employed a much larger spectrum of plants for clinical treatment. Clerodendrum viscosum (CV), a commonly growing weed in the Indian subcontinent has been employed by S. Nirmalananda (Ayurvedic expert) for the treatment of cervical cancer. Here we isolate and characterize a water extract fraction (Cv-AP) from the root of CV and evaluate its anticervical cancer cell bioactivity. Our results indicate that Cv-AP possesses pro-apoptotic, anti-proliferative, and anti-migratory activity in a dose-dependent fashion against cervical cancer cell lines. In contrast, primary fibroblasts (control healthy cells), when exposed to similar concentrations of this extract, fail to undergo apoptosis and remain relatively unaffected. These findings suggest that Clerodendrum viscosum (CV) is a readily available source of components with potent anti-cancer activity and selective bioactivity against cervical cancer cells. The major component in CV-AP was identified as a glycoprotein via SDS Page and Concanavalin-A binding studies. This study serves to illustrate that systematic collaboration with Ayurveda is a practical and powerful strategy in drug discovery and development.

Tetrahedron Letters, 2008

Using Cu(1)-catalyzed [3+2] Huisgen 'click' cycloaddition, a rigid rod -like oligo(p-phenylene vi... more Using Cu(1)-catalyzed [3+2] Huisgen 'click' cycloaddition, a rigid rod -like oligo(p-phenylene vinylene) (OPV) was functionalized at both ends with biotin ligands, combining the valuable electro-optical properties of conjugated organic molecules with the biological recognition capability of biotin. Biotin can be placed at variable distances from the oligomer via appropriate length of a hydrophilic spacer, which also serves to regulate the binding capabilities of the two terminal biotin units. To demonstrate this binding potential, networks were formed with streptavidin-coated quantum dots. The synthetic conditions are presented, together with representative optimizations of the key reactions. The organic compounds were analyzed by means of ATR/FTIR, 1 H NMR (200 or 600 MHz), 13 C NMR, 2D NMR (HMBC, HMQC experiments), MS (ESI or MALDI-TOF), and optical spectroscopy. Networks were imaged with TEM.

ChemInform, 2010

The Concept of a Green Drug: Curcumin and Its Derivatives as a Model System -[45 refs.]. -(RAJA, ... more The Concept of a Green Drug: Curcumin and Its Derivatives as a Model System -[45 refs.]. -(RAJA, K. S.; BALAMBIKA, R.; DOLAI, S.; SHI, W.; Mini-Rev. Org. Chem. 6 (2009) 2, 152-158; Dep. Chem., Coll. Staten Island, City Univ. New York, Staten Island, NY 10301, USA; Eng.) -Lindner 05-255

ACS chemical neuroscience, Jan 21, 2011

The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative of cu... more The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative of curcumin with amplified bioefficacy in modulating amyloid-β and tau peptide aggregation is presented. Curcumin inhibits amyloid-β and tau peptide aggregation at micromolar concentrations; the sugar-curcumin conjugate inhibits Aβ and tau peptide aggregation at concentrations as low as 8 nM and 0.1 nM, respectively. In comparison to curcumin, this conveniently synthesized Alzheimer's drug candidate is a more powerful antioxidant.

Organic Letters, 2007

Curcumin, the primary active ingredient in the spice turmeric, was converted to reactive monofunc... more Curcumin, the primary active ingredient in the spice turmeric, was converted to reactive monofunctional derivatives (carboxylic acid/azide/ alkyne). The derivatives were employed to produce a 3 + 2 azide−alkyne "clicked" curcumin dimer and a poly(amidoamine) (PAMAM) dendrimer− curcumin conjugate. The monofunctional curcumin derivatives retain biological activity and are efficient for labeling and dissolving amyloid fibrils. The curcumin dimer selectively destroys human neurotumor cells. The synthetic methodology developed affords a general strategy for attaching curcumin to various macromolecular scaffolds.

Mini-Reviews in Organic Chemistry, 2009

... I have closely interacted with a Siddha Physician (Dr. Paul Nadar) based ... FORMU-LATIONS, O... more ... I have closely interacted with a Siddha Physician (Dr. Paul Nadar) based ... FORMU-LATIONS, ORGANOMETALLIC COMPLEXES AND CUR-CUMIN DERIVATIVES Formulations Nanoparticles formed by ... Nanocurcumin particles were ~50 nm in size, bioefficacy of this construct ...

Microscopy and Microanalysis, 2008

Combinations of conjugated organic oligomers and inorganic quantum dots bring together the respec... more Combinations of conjugated organic oligomers and inorganic quantum dots bring together the respective valuable opto-electronic properties such as electroluminescence, photoconductivity, and photoluminescence [1-4] for the development of novel applications, e.g. nanoelectronics. Recent efforts in our laboratory lead to the network formation between biotin-functionalized oligo(pphenylene vinylene)s (OPVs) and streptavidin coated quantum dots (Qdots), Scheme 1. We wished to develop a comprehensive microscopic approach involving confocal fluorescence laser scanning microscopy (CFLSM) and transmission electron microscopy (TEM) to understand the formed aggregates structurally and functionally.

International Journal of Cancer, 2014

Current therapies for glioblastoma are largely palliative, involving surgical resection followed ... more Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-jB, P-Akt1, vascular endothelial growth factor, cyclin D1 and BCl XL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-jB conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-jB played a key role in protecting glioblastoma cells. To enhance delivery, we coupled curcumin to the glioblastoma-specific CD68 antibody in a releasable form. This resulted in a 120-fold increase in its efficacy to eliminate GL261 cells. A very similar dose response was also obtained with human glioblastoma lines T98G and U87MG. GL261-implanted mice receiving intratumor infusions of the curcumin-CD68 adduct followed by tail-vein injections of solubilized curcumin displayed a fourfold to fivefold reduction in brain tumor load, survived longer, and about 10% of them lived beyond 100 days. Hematoxylin-eosin staining of brain sections revealed a small scar tissue mass in the rescued mice, indicating adduct-mediated elimination of glioblastoma tumor. The tumor cells were strongly CD681 and some cells in the tumor periphery were strongly positive for microglial Iba1, but weakly positive for CD68. This strategy of antibody targeting of curcumin to tumor comes with the promise of yielding a highly effective therapy for glioblastoma brain tumors.

International Journal of Cancer, 2012

In vitro studies have shown that curcumin, a polyphenol from the culinary component turmeric, has... more In vitro studies have shown that curcumin, a polyphenol from the culinary component turmeric, has strong anticancer properties. However, there is no consensus on its therapeutic effect in human. Our earlier experiments involving implanted murine melanoma B16F10 cells in the neck or brain of syngeneic C57BL6 mice showed that tail vein injection of curcumin blocks formation of lesions and tumor in these mice. However, such treatment was ineffective in eliminating established tumors that already occupied 10% of brain volume. Possible reasons include low solubility and rapid metabolism of curcumin in vivo. To increase its efficacy, we have linked curcumin through a cleavable arm to an antibody (Ab) against the melanoma surface antigen Muc18. The antibody-coupled curcumin was 230-fold more effective in eliminating B16F10 cells in vitro, and in vivo, it rapidly decimated established, B16F10-evoked brain tumors, enabling the rescued mice to live normally far beyond 90 days from implantation of cancer cells. In contrast, mice treated with Muc18 Ab alone died of brain tumor within a month. In B16F10 cells, curcumin-Ab (adduct) treatment caused a dramatic inhibition of NF-kB: a transcription factor that is constitutively activated in cancer cells. Furthermore, overexpression of NF-kB in the B16F10 cells blocked adduct-evoked stimulation of caspase-3/7 activity. Thus, by suppressing NF-kB, the curcumin adduct inhibits other downstream tumor-promoting proteins, thereby eliminating the B16F10 cells. Our study submits a novel yet generally applicable strategy of converting curcumin into a potent anticancer agent and provides a mechanistic framework for its action.

Chemical Communications, 2005

The Cu(I)-catalyzed ATRP and azide-alkyne cycloaddition reactions together provide a versatile me... more The Cu(I)-catalyzed ATRP and azide-alkyne cycloaddition reactions together provide a versatile method for the synthesis of end-functionalized glycopolymers and their attachment to a suitably modified viral protein scaffold.

Biomacromolecules, 2003

Cowpea mosaic virus was derivatized with poly(ethylene glycol) to give well-controlled loadings o... more Cowpea mosaic virus was derivatized with poly(ethylene glycol) to give well-controlled loadings of polymer on the outer surface of the coat protein assembly. The resulting conjugates displayed altered densities and immunogenicities, consistent with the known chemical and biological properties of PEG. These studies make CPMV potentially useful as a tailored vehicle for drug delivery.

Bioconjugate Chemistry, 2009

Azide-terminated poly(tert-butyl acrylate) was synthesized via atom transfer radical polymerizati... more Azide-terminated poly(tert-butyl acrylate) was synthesized via atom transfer radical polymerization (ATRP). Subsequent deprotection was performed to yield poly(acrylic acid) (PAA) possessing a reactive chain-end. A one-pot sequential amidation of the PAA with the amine derivatives of a near-infrared fluorescent dye (ADS832WS) and glucose produced NIRF dye-incorporated water-soluble copolymers. End-group modifications were performed to produce alkyne/biotin-terminated copolymers which were further employed to generate dye-incorporated polymer-protein hybrids via the biotin-avidin interaction with avidin or "click" bioconjugation with azidemodified BSA. We have overcome two fundamental limitations in the synthesis of bioconjugates: (a) the basic restriction in the diversity of copolymers which can be synthesized for producing bioconjugates, (b) the limitation in the number of dyes/drug molecules that can be attached per protein molecule. The copolymers possessed enhanced optical properties compared to the dye due to increased solubility in water. Potential utility of these copolymers and conjugates in multiwell plate based assays, cell surface imaging and in vivo animal imaging were explored.

Bioconjugate Chemistry, 2003

Nonenveloped viruses provide the chemist with large, preassembled polyvalent protein scaffolds fo... more Nonenveloped viruses provide the chemist with large, preassembled polyvalent protein scaffolds for modification. These structures are typically porous to small molecules but not to large ones. The solution-phase structures and reactivities of such assemblies may be substantially different than indicated by X-ray crystal structures. Here, the attachment of organic compounds to either the inside or outside surface of the cowpea mosaic virus (CPMV) coat protein was verified with an indicating antibody-antigen interaction. Antibody binding was subsequently blocked by the installation of poly-(ethylene glycol) chains. These results typify the type of site-specific control that is available with CPMV and related virus building blocks.

Anti-Cancer Agents in Medicinal Chemistry, 2013

Curcumin, which is derived from the plant Curcuma longa, has received considerable attention as a... more Curcumin, which is derived from the plant Curcuma longa, has received considerable attention as a possible anti-cancer agent. In cell culture, curcumin is capable of inducing apoptosis in cancer cells at concentrations that do not affect normal cells. One draw-back holding curcumin back from being an effective anti-cancer agent in humans is that it is almost completely insoluble in water and therefore has poor absorption and subsequently poor bioavailability. Here we have generated a number of curcumin derivatives (tetrahydro-curcumin, curcumin mono-carboxylic acid, curcumin mono-galactose, curcumin mono-alkyne and dendrimer-curcumin conjugate) to test whether any of them display both cytotoxicity and water solubility. Of those tested only dendrimer-curcumin conjugate exhibited both water solubility and cytotoxicity against SKBr3 and BT549 breast cancer cells. When compared to curcumin dissolved in DMSO, dendrimer-curcumin conjugate dissolved in water was significantly more effective in inducing cytotoxicity, as measured by the MTT assay and effectively induced cellular apoptosis measured by caspase-3 activation. Since dendrimer-curcumin conjugate is water soluble and capable of inducing potent cytotoxic effects on breast cancer cell lines, it may prove to be an effective anti-cancer therapy to be used in humans.

Anti-Cancer Agents in Medicinal Chemistry, 2013

The concept of Ayurvedic expert guided drug discovery and development is defined and put to test ... more The concept of Ayurvedic expert guided drug discovery and development is defined and put to test systematically for the first time in literature. Western Science has explored only ~5% of the approximately 25,000 species of higher plants for drug leads. The ancient medical science of Ayurveda has however employed a much larger spectrum of plants for clinical treatment. Clerodendrum viscosum (CV), a commonly growing weed in the Indian subcontinent has been employed by S. Nirmalananda (Ayurvedic expert) for the treatment of cervical cancer. Here we isolate and characterize a water extract fraction (Cv-AP) from the root of CV and evaluate its anticervical cancer cell bioactivity. Our results indicate that Cv-AP possesses pro-apoptotic, anti-proliferative, and anti-migratory activity in a dose-dependent fashion against cervical cancer cell lines. In contrast, primary fibroblasts (control healthy cells), when exposed to similar concentrations of this extract, fail to undergo apoptosis and remain relatively unaffected. These findings suggest that Clerodendrum viscosum (CV) is a readily available source of components with potent anti-cancer activity and selective bioactivity against cervical cancer cells. The major component in CV-AP was identified as a glycoprotein via SDS Page and Concanavalin-A binding studies. This study serves to illustrate that systematic collaboration with Ayurveda is a practical and powerful strategy in drug discovery and development.

Tetrahedron Letters, 2008

Using Cu(1)-catalyzed [3+2] Huisgen 'click' cycloaddition, a rigid rod -like oligo(p-phenylene vi... more Using Cu(1)-catalyzed [3+2] Huisgen 'click' cycloaddition, a rigid rod -like oligo(p-phenylene vinylene) (OPV) was functionalized at both ends with biotin ligands, combining the valuable electro-optical properties of conjugated organic molecules with the biological recognition capability of biotin. Biotin can be placed at variable distances from the oligomer via appropriate length of a hydrophilic spacer, which also serves to regulate the binding capabilities of the two terminal biotin units. To demonstrate this binding potential, networks were formed with streptavidin-coated quantum dots. The synthetic conditions are presented, together with representative optimizations of the key reactions. The organic compounds were analyzed by means of ATR/FTIR, 1 H NMR (200 or 600 MHz), 13 C NMR, 2D NMR (HMBC, HMQC experiments), MS (ESI or MALDI-TOF), and optical spectroscopy. Networks were imaged with TEM.