Conformation of branched polypeptides: The influence of relative position of leucine residues in the side chains

Abstract

Branched polypeptides were synthesized with the general formula poly(Lys-(Xi)) or poly(Lys-(DL-Alam-Xi)), where X = Leu or D-Leu, i < 1, 1 < m < 2. Coupling of Leu or D-Leu to poly(Lys) was achieved by the active ester method. The short DL-Ala oligomers were joined to the side chains by polymerisation of N-carboxy-DL-Ala anhydride. The CD measurements performed in water solutions of various pH and ionic strength indicated that joining Leu or D-Leu directly to Lys ε-amino groups increases dramatically the helix forming tendency. However, this ability was somewhat less pronounced with the D-enantiomer of Leu in accordance with our previous observations concerning the role of configuration. The polypeptide with short DL-Ala oligomers as outside determinants was investigated extensively even in trifluoroethanol-water mixtures and SDS solutions. No significant conformational influence could be demonstrated by the elongation of the branches with 1-2 DL-Ala residues.

Synthesis, Conformation, Biodistribution, and Hormone-Related in Vitro Antitumor Activity of a Gonadotropin-Releasing Hormone Antagonist−Branched Polypeptide Conjugate

“…Synthesis of Branched Polypeptides. (a) Poly[Lys-(Glu i -DL-Ala m )] (EAK), where i ) 0.96 and m ) 3.1, was synthesized as previously described (31) with minor modification using HOBt as a catalyst in the active ester coupling method for the attachment of the glutamic acid residue to the end of the side chains of the branched polypeptide poly[Lys(DL-Ala 3.1 )] (AK) (32). Briefly, poly-(L-Lys) (DP n ) 155) was prepared by the polymerization of N R -carboxy-N -(benzyloxycarbonyl)lysine anhydride.…”

Hogyan befolyásolja a primer szerkezet elágazó láncú polipeptidek térszerkezetét és konjugátumaik funkcionális tulajdonságait?

“…Az X és U aminosav megválasztásával létre lehetett hozni különbözõ töltésû, töltéssûrûségû, hidrofil/ hidrofób karakterû vegyületeket. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] Az MTA Kémiai Tudományok osztálya Oláh György emlékülésén (Budapest, 2017. május 3.) elhangzott elõadás alapján készült jelen össze-foglaló áttekintést nyújt e vegyületek szintézisé-nek stratégiájáról, fõbb lépéseirõl és három különbözõ elágazó láncú vegyületcsoport tanulmá-nyozása során megfigyelt összefüggésekrõl.…”

“…Hasonló viselkedésbeli különbség volt tapasztalható az FAK vs AFK polipeptid pár esetében (pH 3.0, 0.02 M NaCl). 6 Az SAK és ASK polipeptidek oldalláncai protonáltak savas (pH 2.1, 0.02 M NaCl) vizes oldatban és mindkét vegyület konformációja rendezetlen. A pH emelésére (pH 7.2) egyformán reagálnak és részben rendezett konformáció jelenik meg.…”

Side Chain Distribution and Enantiomer Composition of Biodegradable Branched Polypeptides with Polylysine Backbone

“…In order to establish principles applicable for rational design of macromolecular carriers, much emphasis was placed on the chemical^A 13] and biological [14~17] examination of these polymeric polypeptides. The amino-acid composition and sequence of the side chains proved to be important structural features, which can influence in vitro cytotoxicity^, blood clearance^ or immunogenicity^1 5 ' 16 lThe enantiomer composition of the branches might be an additional option to manipulate various biochemical, immunological and pharmacological properties of synthetic carriers (e.g.…”