Amino Acids

, Volume 48, Issue 5, pp 1241–1251 | Cite as

The stereochemical effect of SMAP-29 and SMAP-18 on bacterial selectivity, membrane interaction and anti-inflammatory activity

  • Binu Jacob
  • Ganesan Rajasekaran
  • Eun Young Kim
  • Il-Seon Park
  • Jeong-Kyu BangEmail author
  • Song Yub ShinEmail author
Original Article


Sheep myeloid antimicrobial peptide-29 (SMAP-29) is a cathelicidin-related antimicrobial peptide derived from sheep myeloid cells. In order to investigate the effects of l-to-d-amino acid substitution in SMAP-29 on bacterial selectivity, membrane interaction and anti-inflammatory activity, we synthesized its two d-enantiomeric peptides (SMAP-29-E1 and SMAP-29-E2 containing d-Ile and d-allo-Ile, respectively) and two diastereomeric peptides (SMAP-29-D1 and SMAP-29-D2). Additionally, in order to address the effect of l-to-d-amino acid substitution in the N-terminal helical peptide of SMAP-29 (named SMAP-18) on antimicrobial activity, we synthesized its two d-enantiomeric peptides (SMAP-18-E1 and SMAP-18-E2), which are composed of d-amino acids entirely. l-to-d-amino acid substitution in membrane-targeting AMP, SMAP-29 did not affect its antimicrobial activity. However, d-allo-Ile containing-SMAP-29-E2 and SMAP-29-D2 exhibited less hemolytic activity compared to d-Ile containing-SMAP-29-E1 and SMAP-29-D1, respectively. l-to-d-amino acid substitution in intracellular targeting-AMPs, SMAP-18 and buforin-2 improved antimicrobial activity by 2- to eightfold. The improved antimicrobial activity of the d-isomers of SMAP-18 and buforin-2 seems to be due to the stability against proteases inside bacterial cells. Membrane depolarization and dye leakage suggested that the membrane-disruptive mode of SMAP-29-D1 and SMAP-29-D2 is different from that of SMAP-29, SMAP-29-E1, and SMAP-29-E2. l-to-d-amino acid substitution in SMAP-29 improved anti-inflammatory activity in LPS-stimulated RAW 264.7 cells. In summary, we propose here that d-allo-Ile substitution is a more powerful strategy for increasing bacterial selectivity than d-Ile substitution in the design of d-enantiomeric and diastereomeric AMPs. SMAP-29-D1, and SMAP-29-D2 with improved bacterial selectivity and anti-inflammatory activity can serve as promising candidates for the development of anti-inflammatory and antimicrobial agents.


SMAP-29/SMAP-18 l-to-d-amino acid substitution Bacterial selectivity Anti-inflammatory activity Protease stability 



This study was supported by the research fund from Chosun University, 2015.

Compliance with ethical standards

Conflict of interest

The authors have declared that there is no conflict of interest.


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Binu Jacob
    • 1
  • Ganesan Rajasekaran
    • 1
  • Eun Young Kim
    • 1
  • Il-Seon Park
    • 1
    • 2
  • Jeong-Kyu Bang
    • 3
    Email author
  • Song Yub Shin
    • 1
    • 2
    Email author
  1. 1.Department of Medical Science, Graduate SchoolChosun UniversityGwangjuRepublic of Korea
  2. 2.Department of Cellular and Molecular Medicine, School of MedicineChosun UniversityGwangjuRepublic of Korea
  3. 3.Division of Magnetic ResonanceKorea Basic Science InstituteOchangRepublic of Korea

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