Document 1248
 DOCN  M9591248
 TI    High-resolution solution structure of siamycin II: novel amphipathic
       character of a 21-residue peptide that inhibits HIV fusion.
 DT    9509
 AU    Constantine KL; Friedrichs MS; Detlefsen D; Nishio M; Tsunakawa M;
       Furumai T; Ohkuma H; Oki T; Hill S; Bruccoleri RE; et al; Bristol-Myers
       Squibb Pharmaceutical Research Institute,; Princeton, NJ 08543, USA.
 SO    J Biomol NMR. 1995 Apr;5(3):271-86. Unique Identifier : AIDSLINE
       MED/95307083
 AB    The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I
       (BMY-29304), derived from Streptomyces strains AA3891 and AA6532,
       respectively, have been found to inhibit HIV-1 fusion and viral
       replication in cell culture. The primary sequence of siamycin II is
       CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has
       a valine residue at position 4. In both peptides, disulfide bonds link
       Cys1 with Cys13 and Cys7 with Cys19, and the side chain of Asp9 forms an
       amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50
       mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers
       of cross peaks for a peptide of this size. We have used 335 NOE distance
       constraints and 13 dihedral angle constraints to generate an ensemble of
       30 siamycin II structures; these have average backbone atom and all
       heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 A,
       respectively. The peptide displays an unusual wedge-shaped structure,
       with one face being predominantly hydrophobic and the other being
       predominantly hydrophilic. Chemical shift and NOE data show that the
       siamycin I structure is essentially identical to siamycin II. These
       peptides may act by preventing oligomerization of the HIV transmembrane
       glycoprotein gp41, or by interfering with interactions between gp41 and
       the envelope glycoprotein gp120, the cell membrane or membrane-bound
       proteins [Frechet, D. et al. (1994) Biochemistry, 33, 42-50]. The
       amphipathic nature of siamycin II and siamycin I suggests that a polar
       (or apolar) site on the target protein may be masked by the apolar (or
       polar) face of the peptide upon peptide/protein complexation.
 DE    Amino Acid Sequence  Antibiotics/*CHEMISTRY/PHARMACOLOGY  Antibiotics,
       Peptide/*CHEMISTRY/PHARMACOLOGY  HIV-1/*DRUG EFFECTS  Molecular Sequence
       Data  Nuclear Magnetic Resonance  Protein Conformation
       Streptomyces/CHEMISTRY  Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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