Candidacidal activity prompted by N-terminus histatin-like domain of human salivary mucin (MUC7)

Tarikere L. Gururaja, Joseph H. Levine, Duy T. Tran, Gowda A. Naganagowda, Kalaiyarasi Ramalingam, Narayanan Ramasubbu, Michael J. Levine

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Histidine-rich peptides (histatins, Hsn) in saliva are thought to provide a non-immune defense against Candida albicans. Sequence homology search of the human salivary mucin, MUC7, against histatins revealed a domain at the N-terminus (R3-Q17) having 53% identity to Hsn-5. To determine its candidacidal activity, this 15 residue basic histidine-rich domain of MUC7 (I) was prepared by solid-phase Fmoc chemistry. Various N- and C-terminal protected derivatives of I were also synthesized to correlate the effect of peptide overall charge in exhibiting cidal potency. Candidacidal activity measurement of I and its variants showed considerable ED50 values (effective dosage required to kill 50% of candida cells), albeit greater than Hsn-5 (ED50 ~4-6 μM). Of the various analogs tested, N-terminal free acid (I, ED50 ~40 μM) and amide (V, ED50~16 μM) exhibited appreciable candidacidal activities suggesting the possible role of peptide net charge in cidal action. Blocking of N-terminus with a bulky octanoyl group showed only marginal effect on the cidal activity of I or V, indicating that hydrophobicity of these synthetic constructs may not be important for exerting such activities. Membrane-induced conformational transition from random coil to helical structures of all the test peptides implied their tendency to adapt order structures at the lipid-membrane interface similar to that of Hsn-5. However, comparison of propensity for helical structure formation vs. ED50 indicated that cidal potency of MUC7 Hsn-like peptides depends largely on electrostatic interactions irrespective of secondary structural elements. Delineation of solution structure of the most active peptide (V) by 2D-NMR revealed essentially a non-structured conformation in aqueous medium, which further supported the fact that the peptide helical structure may not be a prerequisite for posing candidacidal activity. The formation of smaller truncated peptides and/or Hsn-like fragments on proteolytic degradation of intact MUC7 in the presence of oral flora provided indirect evidence that mucin could serve as a backup candidacidal agent to salivary Hsn. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)107-119
Number of pages13
JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Issue number1
StatePublished - Apr 12 1999


All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology


  • 2D-NMR
  • Candida albicans
  • Candidacidal activity
  • Circular dichroism
  • Histatin-like domain
  • Human salivary mucin
  • Peptide synthesis
  • Solution conformation

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