Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
Department of Inorganic and Analytical Chemistry, University of Geneva, 24 Quai Ernest Ansermet, CH-1211 4 Geneva, Switzerland.
Biomolecules. 2020 Mar 13;10(3):448. doi: 10.3390/biom10030448.
The structure-activity relationship of branched H-Lys(Arg)-Dab-Dhp-Arg-OH sequence analogues, modified with Cys-Asp or Cys at N-terminal amino acids (Lys, Arg), in VEGF-A/Neuropilin-1 complex inhibition is presented. The addition of Cys residue led to a 100-fold decrease in the IC value, compared to the parent peptide. The change occurred regardless of coupling Cys to the free N-terminal amino group present in the main or the side chain. A few analogues extended by the attachment of Cys at the N-terminus of several potent NRP-1 peptide ligands documented in the literature are also presented. In all studied cases, the enhancement of inhibitory properties after the addition of Cys at the N-terminus is observed. It is particularly evident for the tetrapeptide derived from the C-terminus of VEGF-A (KPRR), suggesting that extending the K/RXXK/R motif (CendR) with the Cys moiety can significantly improve affinity to NRP-1 of CendR peptides.
呈现了带有 Cys-Asp 或 Cys 的支链 H-Lys(Arg)-Dab-Dhp-Arg-OH 序列类似物的结构-活性关系，修饰了 N-末端氨基酸（Lys、Arg）处的 Cys。与母体肽相比，添加 Cys 残基导致 IC 值降低了 100 倍。无论 Cys 与主链或侧链中存在的游离 N-末端氨基基团偶联如何，都会发生这种变化。还呈现了一些通过在文献中报道的几种有效 NRP-1 肽配体的 N-末端添加 Cys 而扩展的类似物。在所有研究的情况下，在 N-末端添加 Cys 后观察到抑制特性的增强。对于源自 VEGF-A（KPRR）C 末端的四肽尤其明显，这表明用 Cys 部分扩展 K/RXXK/R 基序（CendR）可以显著提高 CendR 肽与 NRP-1 的亲和力。
