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Article

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

by
Anna K. Puszko
1,
Piotr Sosnowski
2,
Françoise Raynaud
3,4,5,
Olivier Hermine
3,4,5,
Gérard Hopfgartner
2,
Yves Lepelletier
3,4,5,* and
Aleksandra Misicka
1,6,*
1
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
2
Department of Inorganic and Analytical Chemistry, University of Geneva, 24 Quai Ernest Ansermet, CH-1211 4 Geneva, Switzerland
3
Imagine Institute, Université de Paris, 24 boulevard Montparnasse, 75015 Paris, France
4
INSERM UMR 1163, Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders: Therapeutical Implications, 24 boulevard Montparnasse, 75015 Paris, France
5
CNRS ERL 8254, 24 boulevard Montparnasse, 75015 Paris, France
6
Department of Neuropeptides, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(3), 448; https://doi.org/10.3390/biom10030448
Submission received: 31 January 2020 / Revised: 23 February 2020 / Accepted: 5 March 2020 / Published: 13 March 2020
(This article belongs to the Special Issue Vascular Endothelial Growth Factor (VEGF): From Basic Mechanisms to Clinical Significance and Drug Development)
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Abstract

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-A165/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-A165 (KPRR), suggesting that extending the K/RXXK/R motif (CendR) with the Cys moiety can significantly improve affinity to NRP-1 of CendR peptides.
Keywords: Neuropilin-1; VEGF-A165; VEGF-A165/NRP-1 complex; protein-ligand interaction; peptide ligands Neuropilin-1; VEGF-A165; VEGF-A165/NRP-1 complex; protein-ligand interaction; peptide ligands
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MDPI and ACS Style

Puszko, A.K.; Sosnowski, P.; Raynaud, F.; Hermine, O.; Hopfgartner, G.; Lepelletier, Y.; Misicka, A. Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine. Biomolecules 2020, 10, 448. https://doi.org/10.3390/biom10030448

AMA Style

Puszko AK, Sosnowski P, Raynaud F, Hermine O, Hopfgartner G, Lepelletier Y, Misicka A. Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine. Biomolecules. 2020; 10(3):448. https://doi.org/10.3390/biom10030448

Chicago/Turabian Style

Puszko, Anna K., Piotr Sosnowski, Françoise Raynaud, Olivier Hermine, Gérard Hopfgartner, Yves Lepelletier, and Aleksandra Misicka. 2020. "Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine" Biomolecules 10, no. 3: 448. https://doi.org/10.3390/biom10030448

APA Style

Puszko, A. K., Sosnowski, P., Raynaud, F., Hermine, O., Hopfgartner, G., Lepelletier, Y., & Misicka, A. (2020). Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine. Biomolecules, 10(3), 448. https://doi.org/10.3390/biom10030448

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