Linked Life Data

7918465

Source:http://linkedlifedata.com/resource/pubmed/id/7918465

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
1994-11-10
pubmed:abstractText
Synthesis of the boronic acid analog of the dipeptide Pro-Pro yields a mixture of diastereomers Pro-L-boroPro and Pro-D-boroPro, one of which is a potent inhibitor [Ki = 16 pM; Gutheil, W. G., & Bachovchin, W. W. (1993) Biochemistry 32, 8723-8731] of dipeptidyl amino peptidase type IV (DP IV), also known as CD26. The structures of both diasteremers are determined here in aqueous solution by means of 1D and 2D NMR of 1H, 13C, and 11B, and force-field calculations, and the inhibitor is proven to have the L-L configuration. At low pH values (approximately 2), both diastereomers are trans with respect to the peptide bond. Populations of proline ring conformers are determined by pseudorotation analysis, using vicinal proton spin-coupling constants obtained by computer analysis of 1D1H NMR spectral fine structure. At neutral pH values, the Pro-boroPro inhibitor of DP IV undergoes slow, reversible inactivation (Gutheil & Bachovchin, 1993). By structural determination of the decomposition products of both diasteromers, the process is shown here to involve formation of a six-membered ring between the residues by means of trans-cis conversion and formation of a B-N bond, producing chiral nitrogen atoms in both cases having the S configuration. Analogy to cyclic dipeptides suggests the new compounds be named cyclo(Pro-L-boroPro) and cyclo(Pro-D-boroPro).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12427-38
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Solution structures of active and inactive forms of the DP IV (CD26) inhibitor Pro-boroPro determined by NMR spectroscopy.
pubmed:affiliation
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.