Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine

被引：9

作者：

Puszko, Anna K. ^{[1
]}

Sosnowski, Piotr ^{[2
]}

Raynaud, Francoise ^{[3
,4
,5
]}

Hermine, Olivier ^{[3
,4
,5
]}

Hopfgartner, Gerard ^{[2
]}

Lepelletier, Yves ^{[3
,4
,5
]}

Misicka, Aleksandra ^{[1
,6
]}

机构：

[1] Univ Warsaw, Fac Chem, Pasteura 1, PL-02093 Warsaw, Poland

[2] Univ Geneva, Dept Inorgan & Analyt Chem, 24 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland

[3] Univ Paris, Imagine Inst, 24 Blvd Montparnasse, F-75015 Paris, France

[4] INSERM, UMR 1163, Lab Cellular & Mol Basis Normal Hematopoiesis & H, 24 Blvd Montparnasse, F-75015 Paris, France

[5] CNRS, ERL 8254, 24 Blvd Montparnasse, F-75015 Paris, France

[6] Polish Acad Sci, Dept Neuropeptides, Mossakowski Med Res Ctr, Pawinskiego 5, PL-02106 Warsaw, Poland

来源：

BIOMOLECULES | 2020年 / 10卷 / 03期

关键词：

Neuropilin-1; VEGF-A(165); NRP-1; complex; protein-ligand interaction; peptide ligands; ENDOTHELIAL GROWTH-FACTOR; STRUCTURAL BASIS; HEPARIN-BINDING; TUMOR-CELLS; IN-VITRO; NEUROPILIN-1; RECEPTOR; DOMAIN; ANGIOGENESIS; DEGRADATION;

D O I：

10.3390/biom10030448

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The structure-activity relationship of branched H-Lys(hArg)-Dab-Dhp-Arg-OH sequence analogues, modified with Cys-Asp or Cys at N-terminal amino acids (Lys, hArg), in VEGF-A(165)/Neuropilin-1 complex inhibition is presented. The addition of Cys residue led to a 100-fold decrease in the IC50 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(165) (KPRR), suggesting that extending the K/RXXK/R motif (CendR) with the Cys moiety can significantly improve affinity to NRP-1 of CendR peptides.

引用

页数：11

共 1 条

[1] Structure-activity relationship studies and biological properties evaluation of peptidic NRP-1 ligands: Investigation of N-terminal cysteine importance
Puszko, Anna K.
Sosnowski, Piotr
Hermine, Olivier
Hopfgartner, Gerard
Lepelletier, Yves
Misicka, Aleksandra
BIOORGANIC & MEDICINAL CHEMISTRY, 2023, 94

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