209395-33-5Relevant articles and documents
Glycosylated enfuvirtide: A long-lasting glycopeptide with potent anti-HIV activity
Cheng, Shuihong,Chang, Xuesong,Wang, Yan,Gao, George F.,Shao, Yiming,Ma, Liying,Li, Xuebing
, p. 1372 - 1379 (2015)
Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (T1/2: 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and α-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties.
Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: Potential applications in bioconjugation and targeted drug delivery
Goswami, Lalit N.,Houston, Zachary H.,Sarma, Saurav J.,Jalisatgi, Satish S.,Hawthorne, M. Frederick
, p. 1116 - 1126 (2013/03/28)
Herein we describe the sequential synthesis of a variety of azide-alkyne click chemistry-compatible heterobifunctional oligo(ethylene glycol) (OEG) linkers for bioconjugation chemistry applications. Synthesis of these bioorthogonal linkers was accomplished through desymmetrization of OEGs by conversion of one of the hydroxyl groups to either an alkyne or azido functionality. The remaining distal hydroxyl group on the OEGs was activated by either a 4-nitrophenyl carbonate or a mesylate (-OMs) group. The -OMs functional group served as a useful precursor to form a variety of heterobifunctionalized OEG linkers containing different highly reactive end groups, e.g., iodo, -NH2, -SH and maleimido, that were orthogonal to the alkyne or azido functional group. Also, the alkyne- and azide-terminated OEGs are useful for generating larger discrete poly(ethylene glycol) (PEG) linkers (e.g., PEG 16 and PEG24) by employing a Cu(i)-catalyzed 1,3-dipolar cycloaddition click reaction. The utility of these clickable heterobifunctional OEGs in bioconjugation chemistry was demonstrated by attachment of the integrin (αvβ3) receptor targeting peptide, cyclo-(Arg-Gly-Asp-d-Phe-Lys) (cRGfKD) and to the fluorescent probe sulfo-rhodamine B. The synthetic methodology presented herein is suitable for the large scale production of several novel heterobifunctionalized OEGs from readily available and inexpensive starting materials.
A modular platform for the rapid site-specific radiolabeling of proteins with 18F exemplified by quantitative positron emission tomography of human epidermal growth factor receptor 2
Gill, Herman S.,Tinianow, Jeff N.,Ogasawara, Annie,Flores, Judith E.,Vanderbilt, Alexander N.,Raab, Helga,Scheer, Justin M.,Vandlen, Richard,Williams, Simon-P.,Marik, Jan
experimental part, p. 5816 - 5825 (2010/03/24)
Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional 18F-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing 18F into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [ 18F]FPEGMA, which was used to produce site-specifically 18F-labeled protein (18F-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 ± 3% and a specific activity of 2.2 ( 0.2 Ci/μmol. 18F-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin. 2009 American Chemical Society.
