Gabapentin hybrid peptides and bioconjugates

Iryna Oleksandrivna Lebedyeva; David A. Ostrov; John Neubert; Peter J. Steel; Kunal Patel; Sean M. Sileno; Kevin Goncalves; Mohamed A. Ibrahim; Khalid A. Alamry; Alan R. Katritzky

doi:10.1016/j.bmc.2013.12.017

Gabapentin hybrid peptides and bioconjugates

Iryna Oleksandrivna Lebedyeva, David A. Ostrov, John Neubert, Peter J. Steel, Kunal Patel, Sean M. Sileno, Kevin Goncalves, Mohamed A. Ibrahim, Khalid A. Alamry, Alan R. Katritzky

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Synthetic approaches to gabapentin bioconjugates that overcome the tendency of gabapentin to cyclize into its γ-lactam are studied. Gabapentin was converted by N-acylation at its N-terminus into di-, tri-, and tetrapeptides (L-Ala-Gbp, L-Val-Gbp, L-Ala-L-Phe-Gbp, Gly-L-Ala-β-Ala-Gbp). Carboxyl-activated Boc-protected gabapentin was used to N-, O-, and S-acylate small peptides and hormones to give conjugates that could also provide prodrugs containing conformationally constrained gabapentin units.

Original language	English (US)
Pages (from-to)	1479-1486
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	22
Issue number	4
DOIs	https://doi.org/10.1016/j.bmc.2013.12.017
State	Published - Feb 15 2014
Externally published	Yes

Keywords

Benzotriazole
Coupling
Cyclization
Gabapentin
Peptide

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2013.12.017

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title = "Gabapentin hybrid peptides and bioconjugates",

abstract = "Synthetic approaches to gabapentin bioconjugates that overcome the tendency of gabapentin to cyclize into its γ-lactam are studied. Gabapentin was converted by N-acylation at its N-terminus into di-, tri-, and tetrapeptides (L-Ala-Gbp, L-Val-Gbp, L-Ala-L-Phe-Gbp, Gly-L-Ala-β-Ala-Gbp). Carboxyl-activated Boc-protected gabapentin was used to N-, O-, and S-acylate small peptides and hormones to give conjugates that could also provide prodrugs containing conformationally constrained gabapentin units.",

keywords = "Benzotriazole, Coupling, Cyclization, Gabapentin, Peptide",

author = "Lebedyeva, {Iryna Oleksandrivna} and Ostrov, {David A.} and John Neubert and Steel, {Peter J.} and Kunal Patel and Sileno, {Sean M.} and Kevin Goncalves and Ibrahim, {Mohamed A.} and Alamry, {Khalid A.} and Katritzky, {Alan R.}",

note = "Funding Information: This work was supported by the Kenan Foundation (University of Florida) and the King Abdulaziz University (Saudi Arabia) and Science for Life HHMI Intramural Award. The authors are grateful to Dr. C.D. Hall, Dr. Levan Khelashvili, Professor Said A. El-Feky, Mr. Justin Juelich, Mr. Ashton Innocent, Mr. Bo Nalsen, Mrs. Galyna Vakulenko, Mr. Khanh Ha, and Dr. Joshua Kramer for reading the manuscript, Dr. Jodie Johnson for his help in HLPC–MS analyses, and Dr. M.C.A. Dancel for her help with HRMS analyses. ",

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doi = "10.1016/j.bmc.2013.12.017",

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pages = "1479--1486",

journal = "Bioorganic and Medicinal Chemistry",

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AU - Lebedyeva, Iryna Oleksandrivna

AU - Ostrov, David A.

AU - Neubert, John

AU - Steel, Peter J.

AU - Patel, Kunal

AU - Sileno, Sean M.

AU - Goncalves, Kevin

AU - Ibrahim, Mohamed A.

AU - Alamry, Khalid A.

AU - Katritzky, Alan R.

N1 - Funding Information: This work was supported by the Kenan Foundation (University of Florida) and the King Abdulaziz University (Saudi Arabia) and Science for Life HHMI Intramural Award. The authors are grateful to Dr. C.D. Hall, Dr. Levan Khelashvili, Professor Said A. El-Feky, Mr. Justin Juelich, Mr. Ashton Innocent, Mr. Bo Nalsen, Mrs. Galyna Vakulenko, Mr. Khanh Ha, and Dr. Joshua Kramer for reading the manuscript, Dr. Jodie Johnson for his help in HLPC–MS analyses, and Dr. M.C.A. Dancel for her help with HRMS analyses.

PY - 2014/2/15

Y1 - 2014/2/15

N2 - Synthetic approaches to gabapentin bioconjugates that overcome the tendency of gabapentin to cyclize into its γ-lactam are studied. Gabapentin was converted by N-acylation at its N-terminus into di-, tri-, and tetrapeptides (L-Ala-Gbp, L-Val-Gbp, L-Ala-L-Phe-Gbp, Gly-L-Ala-β-Ala-Gbp). Carboxyl-activated Boc-protected gabapentin was used to N-, O-, and S-acylate small peptides and hormones to give conjugates that could also provide prodrugs containing conformationally constrained gabapentin units.

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KW - Coupling

KW - Cyclization

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KW - Peptide

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Gabapentin hybrid peptides and bioconjugates

Abstract

Keywords

ASJC Scopus subject areas

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