Gabapentin hybrid peptides and bioconjugates.
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.
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
Iryna O
IO
Lebedyeva
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32611, USA.
David A
DA
Ostrov
Department of Orthodontics, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
John
J
Neubert
Chemistry Department, University of Canterbury, Christchurch 8140, New Zealand.
Peter J
PJ
Steel
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
Kunal
K
Patel
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
Sean M
SM
Sileno
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
Kevin
K
Goncalves
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
Mohamed A
MA
Ibrahim
Chemistry Department, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Khalid A
KA
Alamry
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: katritzky@chem.ufl.edu.
Alan R
AR
Katritzky
D000215:Acylation; D000588:Amines / Q000737:chemistry*; D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018360:Crystallography, X-Ray; D003500:Cyclization; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D004195:Disease Models, Animal; D000077206:Gabapentin; D051379:Mice; D008968:Molecular Conformation; D010146:Pain / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000737:chemistry*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D010455:Peptides; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
Benzotriazole; Coupling; Cyclization; Gabapentin; Peptide