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 journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1479-1486
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number4
DOIs
StatePublished - Feb 15 2014
Externally publishedYes

Fingerprint

glycyl-alanyl-phenylalanine
Peptides
Lactams
Acylation
Peptide Hormones
Prodrugs
gabapentin

Keywords

  • Benzotriazole
  • Coupling
  • Cyclization
  • Gabapentin
  • Peptide

ASJC Scopus subject areas

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

Cite this

Lebedyeva, I. O., Ostrov, D. A., Neubert, J., Steel, P. J., Patel, K., Sileno, S. M., ... Katritzky, A. R. (2014). Gabapentin hybrid peptides and bioconjugates. Bioorganic and Medicinal Chemistry, 22(4), 1479-1486. https://doi.org/10.1016/j.bmc.2013.12.017

Gabapentin hybrid peptides and bioconjugates. / Lebedyeva, Iryna Oleksandrivna; Ostrov, David A.; Neubert, John; Steel, Peter J.; Patel, Kunal; Sileno, Sean M.; Goncalves, Kevin; Ibrahim, Mohamed A.; Alamry, Khalid A.; Katritzky, Alan R.

In: Bioorganic and Medicinal Chemistry, Vol. 22, No. 4, 15.02.2014, p. 1479-1486.

Research output: Contribution to journalArticle

Lebedyeva, IO, Ostrov, DA, Neubert, J, Steel, PJ, Patel, K, Sileno, SM, Goncalves, K, Ibrahim, MA, Alamry, KA & Katritzky, AR 2014, 'Gabapentin hybrid peptides and bioconjugates', Bioorganic and Medicinal Chemistry, vol. 22, no. 4, pp. 1479-1486. https://doi.org/10.1016/j.bmc.2013.12.017
Lebedyeva IO, Ostrov DA, Neubert J, Steel PJ, Patel K, Sileno SM et al. Gabapentin hybrid peptides and bioconjugates. Bioorganic and Medicinal Chemistry. 2014 Feb 15;22(4):1479-1486. https://doi.org/10.1016/j.bmc.2013.12.017
Lebedyeva, Iryna Oleksandrivna ; Ostrov, David A. ; Neubert, John ; Steel, Peter J. ; Patel, Kunal ; Sileno, Sean M. ; Goncalves, Kevin ; Ibrahim, Mohamed A. ; Alamry, Khalid A. ; Katritzky, Alan R. / Gabapentin hybrid peptides and bioconjugates. In: Bioorganic and Medicinal Chemistry. 2014 ; Vol. 22, No. 4. pp. 1479-1486.
@article{ce15c2dfebaf4de0ad0021f687cab77f,
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.}",
year = "2014",
month = "2",
day = "15",
doi = "10.1016/j.bmc.2013.12.017",
language = "English (US)",
volume = "22",
pages = "1479--1486",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - Gabapentin hybrid peptides and bioconjugates

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.

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.

AB - 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.

KW - Benzotriazole

KW - Coupling

KW - Cyclization

KW - Gabapentin

KW - Peptide

UR - http://www.scopus.com/inward/record.url?scp=84893739328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893739328&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2013.12.017

DO - 10.1016/j.bmc.2013.12.017

M3 - Article

C2 - 24468631

AN - SCOPUS:84893739328

VL - 22

SP - 1479

EP - 1486

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 4

ER -