Amide proton exchange rates of a bound pepsin inhibitor determined by isotope-edited proton NMR experiments
Journal Article
·
· Biochem. Biophys. Res. Commun.; (United States)
From a series of isotope-edited proton NMR spectra, amide proton exchange rates were measured at 20 C, 30 C, and 40/sup 0/C for a tightly bound /sup 15/N-labeled tripeptide inhibitor of porcine pepsin (IC50 = 1.7 X 10(-) M). Markedly different NH exchange rates were observed for the three amide protons of the bound inhibitor. The P1 NH exchanged much more slowly than the P2 NH and P3 NH. These results are discussed in terms of the relative solvent accessibility in the active site and the role of the NH protons of the inhibitor for hydrogen bonding to the enzyme. In this study a useful approach is demonstrated for obtaining NH exchange rates on ligands bound to biomacromolecules, the knowledge of which could be of potential utility in the design of therapeutically useful nonpeptide enzyme inhibitors from peptide leads.
- Research Organization:
- Abbott Laboratories, Abbott Park, IL
- OSTI ID:
- 5856966
- Journal Information:
- Biochem. Biophys. Res. Commun.; (United States), Journal Name: Biochem. Biophys. Res. Commun.; (United States) Vol. 147:3; ISSN BBRCA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID PROTEINASES
AMIDES
ANIMALS
BARYONS
DOMESTIC ANIMALS
ELEMENTARY PARTICLES
ENZYME INHIBITORS
ENZYMES
FERMIONS
HADRONS
HYDROLASES
ION EXCHANGE
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
NITROGEN 15
NITROGEN ISOTOPES
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEONS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPSIN
PEPTIDE HYDROLASES
PROTONS
RESONANCE
SPECTRA
STABLE ISOTOPES
STRUCTURE-ACTIVITY RELATIONSHIPS
SWINE
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
ACID PROTEINASES
AMIDES
ANIMALS
BARYONS
DOMESTIC ANIMALS
ELEMENTARY PARTICLES
ENZYME INHIBITORS
ENZYMES
FERMIONS
HADRONS
HYDROLASES
ION EXCHANGE
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
NITROGEN 15
NITROGEN ISOTOPES
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEONS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPSIN
PEPTIDE HYDROLASES
PROTONS
RESONANCE
SPECTRA
STABLE ISOTOPES
STRUCTURE-ACTIVITY RELATIONSHIPS
SWINE
VERTEBRATES