Carrier design: Synthesis and conformational studies of poly (L-lysine) based branched polypeptides with hydroxyl groups in the side chains

Autor: Gábor Mezö, Ildikó B. Nagy, Ferenc Hudecz, Judit Kajtár, Mária Szekerke
Rok vydání: 1997
Předmět:
Zdroj: Biopolymers. 42:719-730
ISSN: 1097-0282
0006-3525
Popis: In the present study the development of a new series of branched polypeptides that contain hydroxyl groups in side chains is reported. Serine or threonine were attached by 1-hydroxy-benzotriazole catalyzed active ester method to the N-terminals of oligo (DL-alanine) chains grafted to a polylysine backbone resulted in poly[Lys-(Ser1-DL-Alam)] (SAK) and poly-[Lys-(Thri-DL-Alam)] (TAK). Ser was coupled also directly to the η-amino groups of polylysine followed by polymerization of N-carboxy-DL-alanine anhydride resulting oligo (DL-Ala) chain terminals. In this way a reverse sequence was built up in the side chain corresponding to the poly[Lys-(DL-Alam-Seri)] (ASK). The number of hydroxyl groups in the polymer was increased by the synthesis of a branched polypeptide with oligo (DL-serine) branches instead of oligo (DL-alanine) ones—poly[Lys-(DL-Serm)] (SK). Classification of solution conformations of branched polypeptides was carried out by CD spectroscopy performed in water solution of various pH values and ionic strengths. Incorporation of single Ser residues in poly[Lys-(Xi)]-type polypeptides markedly promotes the formation of ordered structure without resulting precipitation even in high salt concentration. The presence of branches with multiple DL-Ser residues resulted in a slightly decreased ability of the polypeptide backbone to adopt an ordered conformation. Comparison of the CD properties of the SAK-ASK pair demonstrates that these compounds are similar, showing an increased tendency to form an ordered spatial arrangement in solution at elevated pH or ionic strength; however, differences in their CD spectra suggest that SAK has higher capability to form regular conformation under comparable conditions. The replacement of Ser by the Thr residue in poly[Lys-(Xi-DL-Alam)] induced a conformational transition and TAK exhibited a more helical structure. These results might indicate that not only hydrophobic or ionic attraction, but also H-bond interaction, can play a role in the formation and/or stabilization of ordered conformation of branched polypeptides. Findings with the hydroxyl group containing polymers reported in this paper can also explain their prolonged shelf stability and high water solubility. © 1997 John Wiley & Sons, Inc. Biopoly 42: 719–730, 1997
Databáze: OpenAIRE
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