Noncovalent Peptide Stapling Using Alpha-Methyl-l-Phenylalanine for α-Helical Peptidomimetics
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Other documents of the author: Bathgate, Ross A. D.; Praveen, Praveen; Sethi, Ashish; Dhingra, Rishi R.; Kocan, Martina; Ou, Qinghao; Valkovic, Adam L.,; Gil-Miravet, Isis; Navarro Sánchez, Mónica; Olucha-Bordonau, Francisco E; Gundlach, Andrew Lawrence; Rosengren, K. Johan; Dutschmann, Mathias; Hossain, Mohammed Akhter
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Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/36080
comunitat-uji-handle3:10234/36082
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INVESTIGACIONMetadata
Title
Noncovalent Peptide Stapling Using Alpha-Methyl-l-Phenylalanine for α-Helical PeptidomimeticsAuthor (s)
Date
2023-08-20Publisher
American Chemical SocietyISSN
0002-7863; 1520-5126Bibliographic citation
Bathgate, Ross A. D., Praveen, Praveen, Sethi, Ashish, Furuya, Werner I., Dhingra, Rishi R., Kocan, Martina, Ou, Qinghao, Valkovic, Adam L., Gil-Miravet, Isis, Navarro-Sánchez, Mónica, Olucha-Bordonau, Francisco E., Gundlach, Andrew L., Rosengren, K. Johan, Gooley, Paul R., Dutschmann, Mathias, and Hossain, Mohammed Akhter (2023). Noncovalent peptide stapling using alpha-methyl-l-phenylalanine for α-helical peptidomimetics. Journal of the American Chemical Society 145 (37) 20242-20247. https://doi.org/10.1021/jacs.3c02743Type
info:eu-repo/semantics/articlePublisher version
https://pubs.acs.org/doi/full/10.1021/jacs.3c02743Version
info:eu-repo/semantics/acceptedVersionSubject
Abstract
Peptides and peptidomimetics are attractive drug candidates because of their high target specificity and low-toxicity profiles. Developing peptidomimetics using hydrocarbon (HC)-stapling or other stapling strategies ... [+]
Peptides and peptidomimetics are attractive drug candidates because of their high target specificity and low-toxicity profiles. Developing peptidomimetics using hydrocarbon (HC)-stapling or other stapling strategies has gained momentum because of their high stability and resistance to proteases; however, they have limitations. Here, we take advantage of the α-methyl group and an aromatic phenyl ring in a unique unnatural amino acid, α-methyl-l-phenylalanine (αF), and propose a novel, noncovalent stapling strategy to stabilize peptides. We utilized this strategy to create an α-helical B-chain mimetic of a complex insulin-like peptide, human relaxin-3 (H3 relaxin). Our comprehensive data set (in vitro, ex vivo, and in vivo) confirmed that the new high-yielding B-chain mimetic, H3B10-27(13/17αF), is remarkably stable in serum and fully mimics the biological function of H3 relaxin. H3B10-27(13/17αF) is an excellent scaffold for further development as a drug lead and an important tool to decipher the physiological functions of the neuropeptide G protein-coupled receptor, RXFP3. [-]
Is part of
Journal of the American Chemical Society, 2023, vol. 145, no 37Funder Name
National Health and Medical Research Council (NHMRC) (Australia) | NHMRC Fellowship | Ministerio de Ciencia, Innovación y Universidades | Universitat Jaume I
Funder ID
http://dx.doi.org/10.13039/501100011033
Project code
1182996 | 2001278 | 1165801 | 2001027 | 1042650 | MICIU/ICTI2017-2020/RTI2018-095698-B-I00 | POSDOC/2021/19 | PREDOC/2021/19
Project title or grant
Desarrollo de sistemas peptidérgicos relacionados con comportamiento social. la interacción relaxin3-oxitocina
Rights
Copyright © American Chemical Society
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info:eu-repo/semantics/embargoedAccess
http://rightsstatements.org/vocab/CNE/1.0/
info:eu-repo/semantics/embargoedAccess
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- MED_Articles [669]