General Route toward Side-Chain-Functionalized α-Helical Polypeptides

• Published in: Biomacromolecules Vol. 11; no. 6; pp. 1585 - 1592
• Main Authors: Tang, Haoyu, Zhang, Donghui
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 14.06.2010; Amer Chemical Soc
• Subjects: Aminoacid polymers; Applied sciences; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Circular Dichroism; Exact sciences and technology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mannose - chemistry; Molecular Weight; Organosilicon Compounds - chemistry; Peptides - chemical synthesis; Peptides - chemistry; Physical Sciences; Physicochemistry of polymers; Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - chemical synthesis; Polyglutamic Acid - chemistry; Polymer Science; Protein Conformation; Science & Technology; Solutions; Synthetic biopolymers; DESIGN; 1ST SYNTHESIS; GLYCOPOLYMERS; CLICK CHEMISTRY; FOLDAMERS; DYNAMICS; RING-OPENING POLYMERIZATION; COPOLYMERS; N-CARBOXYANHYDRIDES; COMBINATION; Ring opening polymerization; 1,3-Dipolar cycloaddition; Alkyl glutamate polymer; Aldose; Experimental study; Aminoacid polymer; Thermal stability; Organic solution; Glycopolymer; Azides; Solid state; Monodispersed polymer; Chemical modification; Preparation; Soluble compound; Helical structure; Chlorine containing polymer; Aqueous solution; Nucleophilic substitution; Conformation
• ISSN: 1525-7797; 1526-4602; 1526-4602
• DOI: 10.1021/bm1002174

A series of poly(γ-chloropropyl-l-glutamate) (PCPLG) with controlled polymer molecular weight (MW = 5−28 kg·mol−1) and molecular weight distribution (PDI = 1.16−1.26) have been prepared from hexamethyldisilazane (HMDS)-mediated ring-opening polymerization (ROP) of γ-chloropropyl-l-glutamic acid based N-carboxylanhydride (CP-NCA). CD, FTIR, and WAXS analysis reveal that the polymers adopt α-helical conformations both in solution and the solid state. Their helical surfaces can be readily decorated with functional moieties to confer desired properties, as demonstrated by the quantitative derivatization of the PCPLG side chains with azido functional groups that are amendable to “click” chemistry. Subsequent side-chain conjugation with mannose moieties via copper-mediated [2 + 3] alkyne−azide 1,3-dipolar cycloaddition affords water-soluble mannose−polypeptide conjugates with quantitative grafting efficiency occurring under mild conditions. CD analysis reveals that the mannose−polypeptide conjugates also retain α-helical conformations in aqueous solution.