N -Methylated Cyclic RGD Peptides as Highly Active and Selective α V β 3 Integrin Antagonists
Abstract
The alpha(V)beta(3) integrin receptor plays an important role in human tumor metastasis and tumor-induced angiogenesis. The in vivo inhibition of this receptor by antibodies or by cyclic peptides containing the RGD sequence may in the future be used to selectively suppress these diseases. Here we investigate the influence of N-methylation of the active and selective alpha(V)beta(3) antagonist cyclo(RGDfV) (L1) on biological activity. Cyclo(RGDf-N(Me)V-) (P5) was found to be even more active than L1 and is one of the most active and selective compounds in inhibiting vitronectin binding to the alpha(V)beta(3) integrin. Its high-resolution, three-dimensional structure in water was determined by NMR techniques, distance geometry calculations, and molecular dynamics calculations, providing more insight into the structure-activity relationship.
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Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels
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Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors
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Self-citation
- Authors
- Dechantsreiter, M. A., Planker, E., Mathä, B., Lohof, E., Hölzemann, G., Jonczyk, A., Goodman, S. L., & Kessler, H.
- Affiliations
- Merck KGaA, Darmstadt (Germany) (DE)
- Corresponding author
- Kessler, Horst
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1999-07-24
- Volume
- 42
- Issue
- 16
- Pages
- 3033-3040
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2065097700
- Cited by
- 838
- References
- 1
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 19 · 2023: 14 · 2022: 14 · 2021: 25 · 2020: 21 · 2019: 31 · 2018: 41 · 2017: 39 · 2016: 26 · 2015: 41 · 2014: 38 · 2013: 49 · 2012: 45
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- integrin αvβ3, RGD peptide, N-methylation, integrin antagonists, vitronectin binding, metastasis, tumor angiogenesis, structure-activity relationship
- MeSH terms
- Humans, Ligands, Methylation, Models, Molecular, Molecular Conformation, Magnetic Resonance Spectroscopy, Oligopeptides, Peptides, Cyclic, Snake Venoms, Integrins
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