Optimization of RGD-containing cyclic peptides against αvβ3 integrin

Yan Wang, Wenwu Xiao, Yonghong Zhang, Leah Meza, Harry Tseng, Yoshikazu Takada, James B. Ames, Kit Lam

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp-containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity. αvβ3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure-activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against αvβ3 integrin-transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing αvβ3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress αvβ3 integrin.

Original languageEnglish (US)
Pages (from-to)232-240
Number of pages9
JournalMolecular Cancer Therapeutics
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Cyclic Peptides
Integrins
Neoplasms
Vascular Tissue Neoplasms
Peptide Library
K562 Cells
Structure-Activity Relationship
Glioblastoma
Heterografts
Nude Mice
Disulfides
Ligands
Technology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Optimization of RGD-containing cyclic peptides against αvβ3 integrin. / Wang, Yan; Xiao, Wenwu; Zhang, Yonghong; Meza, Leah; Tseng, Harry; Takada, Yoshikazu; Ames, James B.; Lam, Kit.

In: Molecular Cancer Therapeutics, Vol. 15, No. 2, 01.02.2016, p. 232-240.

Research output: Contribution to journalArticle

Wang, Yan ; Xiao, Wenwu ; Zhang, Yonghong ; Meza, Leah ; Tseng, Harry ; Takada, Yoshikazu ; Ames, James B. ; Lam, Kit. / Optimization of RGD-containing cyclic peptides against αvβ3 integrin. In: Molecular Cancer Therapeutics. 2016 ; Vol. 15, No. 2. pp. 232-240.
@article{237a4a5e4ab048e6bfb795cafa42b334,
title = "Optimization of RGD-containing cyclic peptides against αvβ3 integrin",
abstract = "We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp-containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity. αvβ3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure-activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against αvβ3 integrin-transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing αvβ3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress αvβ3 integrin.",
author = "Yan Wang and Wenwu Xiao and Yonghong Zhang and Leah Meza and Harry Tseng and Yoshikazu Takada and Ames, {James B.} and Kit Lam",
year = "2016",
month = "2",
day = "1",
doi = "10.1158/1535-7163.MCT-15-0544",
language = "English (US)",
volume = "15",
pages = "232--240",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - Optimization of RGD-containing cyclic peptides against αvβ3 integrin

AU - Wang, Yan

AU - Xiao, Wenwu

AU - Zhang, Yonghong

AU - Meza, Leah

AU - Tseng, Harry

AU - Takada, Yoshikazu

AU - Ames, James B.

AU - Lam, Kit

PY - 2016/2/1

Y1 - 2016/2/1

N2 - We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp-containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity. αvβ3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure-activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against αvβ3 integrin-transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing αvβ3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress αvβ3 integrin.

AB - We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp-containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity. αvβ3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure-activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against αvβ3 integrin-transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing αvβ3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress αvβ3 integrin.

UR - http://www.scopus.com/inward/record.url?scp=84960381048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960381048&partnerID=8YFLogxK

U2 - 10.1158/1535-7163.MCT-15-0544

DO - 10.1158/1535-7163.MCT-15-0544

M3 - Article

C2 - 26719578

AN - SCOPUS:84960381048

VL - 15

SP - 232

EP - 240

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 2

ER -