Document 3238
 DOCN  M94A3238
 TI    Properties of the enzyme dipeptidyl peptidase IV (DPP IV/CD26) from a
       chemical viewpoint.
 DT    9412
 AU    Barth A; Neubert K; Born I; Heins J; Faust J; Rahfeld J; Brandt W;
       Hovanessian AG; A.G.M.V. Institute of Biochemistry, University of Halle,
       Germany.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):121 (abstract no. PA0103). Unique
       Identifier : AIDSLINE ICA10/94369337
 AB    DPP IV/CD26 hydrolyzes dipeptide units from the N-termini of peptides
       and proteins, preferable at the C-terminal side of proline residues. A
       substrate is recognized when the N-terminal amino group is protonated
       (positive changed). The best substrates are when in the P1-position is a
       proline or a alanine residue, whereas the P2-position can be any amino
       acyl residue. In a Xaa-Pro-Yaa tripeptide when the Yaa is a proline or a
       hydroxyproline residue (P'1-position), then it is not recognized as a
       substrate. The stereospecificity in the P1-position is absolute, whereas
       that in the P2-position is relative, depending from the amino acid
       residue in the P1-position. Molecular modeling studies give insights
       into the possible recognition conformation of substrate molecules,
       including the distribution of the positive and negative electrostatic
       potential on the surface of such molecules, and some hints about the
       possible structure of the catalytic center of the enzyme DPP IV/CD26. In
       view of this knowledge, it is possible to develop some dipeptides or
       amino acid derivatives which are potent reversible inhibitors of the DPP
       IV/CD26 activity. A condition for the generation of the inhibitory
       potential is the protonisation of the N-terminal amino function, that
       means the formation of a positive potential in this area, and in the
       meantime suppression of the negative charge (negative potential) on the
       C-terminal end of a dipeptide. In agreement with this, the most potent
       inhibitor of such class of compounds is isoleucine-pyrrolidide with a
       Ki-value of about 10(-7) M at pH 6.3. Since CD26 is the coreceptor of
       CD4 which is required for HIV entry into cells, then current work is
       directed on the potential inhibitory effect of DPP IV-specific compounds
       on the HIV infection.
 DE    Amino Acid Sequence  Antigens, CD/DRUG EFFECTS/PHYSIOLOGY  Antigens,
       CD4/DRUG EFFECTS/PHYSIOLOGY  Antigens, Differentiation,
       T-Lymphocyte/DRUG EFFECTS/PHYSIOLOGY  Antiviral Agents/*PHARMACOLOGY
       Comparative Study  Dipeptides/*PHARMACOLOGY  Dipeptidyl
       Peptidases/*METABOLISM  Human  HIV/DRUG EFFECTS/*PHYSIOLOGY  Models,
       Molecular  Molecular Sequence Data  Oligopeptides/CHEMISTRY/METABOLISM
       Protease Inhibitors/*PHARMACOLOGY  Protein Conformation  Substrate
       Specificity  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).