Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted Cαamino acids

Rickey Paige Hicks

Research output: Contribution to journalArticle

10 Scopus citations


Eleven antimicrobial peptides (AMP) based on the incorporation of cyclic tetra substituted Cαamino acids, as well as other unnatural amino acids were designed, synthesized and screened for in vitro activity against 18 strains of bacteria as well as 12 cancer cell lines. The AMPs discussed herein are derived from the following peptide sequence: Ac-GF(X)G(X)B(X)G(X)F(X)G(X)GB(X)BBBB-amide, X = any one of the following residues, A5c, A6c, Tic or Oic and B = any one of the following residues, Arg, Lys, Orn, Dpr or Dab. A diversity of in vitro inhibitory activity was observed for these AMPs. Several analogs exhibited single digit μM activity against drug resistant bacteria including; multiple drug resistant Mycobacterium tuberculosis, extremely drug resistant Mycobacterium tuberculosis and MRSA. The physicochemical properties of the basic amino acid residues incorporated into these AMPs seem to play a major role in defining antibacterial activity. Overall hydrophobicity seems to play a limited role in defining antibacterial activity. The ESKAPE pathogens were used to compare the activity of these AMPs to another family of synthetic AMPs incorporating the unnatural amino acids Tic and Oic. In most cases similarly substituted members of both families exhibited similar inhibitory activity against the ESKAPE pathogens. In specific cases differences in activity as high as 15 fold were observed between analogs. In addition four of these AMPs exhibited promising IC50(<7.5 μM) values against 12 different and diverse cancer cell lines. Five other AMPs exhibited promising IC50(<7.5 μM) values against selected cancer cell lines.

Original languageEnglish (US)
Pages (from-to)4056-4065
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number18
StatePublished - Jan 1 2016



  • AMP
  • Antibacterial
  • Anticancer
  • Cyclic tetra-substituted Camino acids
  • Drug resistant Mycobacterium tuberculosis
  • Unnatural amino acids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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