Gabapentin hybrid peptides and bioconjugates

Iryna O 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

Bioorg Med Chem. 2014 Feb 15;22(4):1479-86. doi: 10.1016/j.bmc.2013.12.017. Epub 2013 Dec 12.

Authors

Affiliations

¹ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
² Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32611, USA.
³ Department of Orthodontics, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
⁴ Chemistry Department, University of Canterbury, Christchurch 8140, New Zealand.
⁵ Chemistry Department, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA; Chemistry Department, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: [email protected].

PMID: 24468631
DOI: 10.1016/j.bmc.2013.12.017

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acylation
Amines / chemistry*
Analgesics / chemistry*
Analgesics / pharmacology
Analgesics / therapeutic use
Animals
Behavior, Animal / drug effects
Crystallography, X-Ray
Cyclization
Cyclohexanecarboxylic Acids / chemistry*
Disease Models, Animal
Gabapentin
Mice
Molecular Conformation
Pain / drug therapy
Peptides / chemistry*
gamma-Aminobutyric Acid / chemistry*

Substances

Amines
Analgesics
Cyclohexanecarboxylic Acids
Peptides
gamma-Aminobutyric Acid
Gabapentin