Efficacy Evaluation of SDF-1α-Based Polypeptides in an Acute Myocardial Infarction Model Using Structure-Based Drug Design

Kang Gon Lee, Ana Rita M.P. Santos, Yong Guk Kang, Yun Jin Chae, Masaud Shah, Rameez Hassan Pirzada, Myeongjin Song, Jongseong Kim, Sangdun Choi, Yongdoo Park

Research output: Contribution to journalArticlepeer-review

Abstract

Stromal cell-derived factor-1 alpha (SDF-1α, CXCL12) mediates the migration of circulating cells to desired sites for tissue development, homeostasis, and regeneration and can be used to promote cardiac regeneration by recruiting stem cells. However, the use of SDF-1α in the injured heart necessitates not only higher binding affinity to its receptor, CXCR4+, but also better robustness against enzymatic degradation than other SDF-1 isoforms. Here, we conduct a screening of SDF-1α analog peptides that were designed by structure-based drug design (SBDD), a type of computer-aided drug design (CADD). We have developed in vitro and in vivo methods that enable us to estimate the effect of peptides on the migration of human mesenchymal stem cells (hMSCs) and cardiac regeneration in acute myocardial infarction (AMI)-induced animals, respectively. We demonstrate that one type of SDF-1α analog peptide, SDP-4, among the four analog peptides preselected by SBDD, is more potent than native SDF-1α for cardiac regeneration in myocardial infarction. It is interesting to note that the migratory effects of SDP-4 determined by a wound healing assay, a Transwell assay, and a 2D migration assay are comparable to those of SDF-1α. These results suggest that in vivo, as well as in vitro, screening of peptides developed by SBDD is a quintessential process to the development of a novel therapeutic compound for cardiac regeneration. Our finding also has an implication that the SDP-4 peptide is an excellent candidate for use in the regeneration of an AMI heart.

Original languageEnglish
Pages (from-to)4486-4496
Number of pages11
JournalACS Biomaterials Science and Engineering
Volume8
Issue number10
DOIs
Publication statusPublished - 2022 Oct 10

Keywords

  • acute myocardial infarction (AMI)
  • computer-aided drug design (CADD)
  • hyaluronic acid-based hydrogel (HA gels)
  • stromal cell-derived factor-1 alpha (SDF-1α)
  • structure-based drug design (SBDD)

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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