TY - JOUR

T1 - Conformational properties, membrane interaction, and antibacterial activity of the peptaibiotic chalciporin a

T2 - Multitechnique spectroscopic and biophysical investigations on the natural compound and labeled analogs

AU - Biondi, Barbara

AU - Peggion, Cristina

AU - De Zotti, Marta

AU - Pignaffo, Chiara

AU - Dalzini, Annalisa

AU - Bortolus, Marco

AU - Oancea, Simona

AU - Hilma, Geta

AU - Bortolotti, Annalisa

AU - Stella, Lorenzo

AU - Pedersen, Jens Z.

AU - Syryamina, Victoria N.

AU - Tsvetkov, Yuri D.

AU - Dzuba, Sergei A.

AU - Toniolo, Claudio

AU - Formaggio, Fernando

N1 - Publisher Copyright: © 2017VC Wiley Periodicals, Inc. .

PY - 2018/9

Y1 - 2018/9

N2 - In this work, an extensive set of spectroscopic and biophysical techniques (including FT-IR absorption, CD, 2D-NMR, fluorescence, and CW/PELDOR EPR) was used to study the conformational preferences, membrane interaction, and bioactivity properties of the naturally occurring synthetic 14-mer peptaibiotic chalciporin A, characterized by a relatively low (≈20%), uncommon proportion of the strongly helicogenic Aib residue. In addition to the unlabeled peptide, we gained in-depth information from the study of two labeled analogs, characterized by one or two residues of the helicogenic, nitroxyl radical-containing TOAC. All three compounds were prepared using the SPPS methodology, which was carefully modified in the course of the syntheses of TOAC-labeled analogs in view of the poorly reactive a-amino function of this very bulky residue and the specific requirements of its free-radical side chain. Despite its potentially high flexibility, our results point to a predominant, partly amphiphilic, a-helical conformation for this peptaibiotic. Therefore, not surprisingly, we found an effective membrane affinity and a remarkable penetration propensity. However, chalciporin A exhibits a selectivity in its antibacterial activity not in agreement with that typical of the other members of this peptide class.

AB - In this work, an extensive set of spectroscopic and biophysical techniques (including FT-IR absorption, CD, 2D-NMR, fluorescence, and CW/PELDOR EPR) was used to study the conformational preferences, membrane interaction, and bioactivity properties of the naturally occurring synthetic 14-mer peptaibiotic chalciporin A, characterized by a relatively low (≈20%), uncommon proportion of the strongly helicogenic Aib residue. In addition to the unlabeled peptide, we gained in-depth information from the study of two labeled analogs, characterized by one or two residues of the helicogenic, nitroxyl radical-containing TOAC. All three compounds were prepared using the SPPS methodology, which was carefully modified in the course of the syntheses of TOAC-labeled analogs in view of the poorly reactive a-amino function of this very bulky residue and the specific requirements of its free-radical side chain. Despite its potentially high flexibility, our results point to a predominant, partly amphiphilic, a-helical conformation for this peptaibiotic. Therefore, not surprisingly, we found an effective membrane affinity and a remarkable penetration propensity. However, chalciporin A exhibits a selectivity in its antibacterial activity not in agreement with that typical of the other members of this peptide class.

KW - Biological activity

KW - Chalciporin

KW - Conformation

KW - Membrane penetration

KW - Peptaibiotics

KW - membrane penetration

KW - TRYPTOPHAN

KW - biological activity

KW - peptaibiotics

KW - VIBRATIONAL CIRCULAR-DICHROISM

KW - chalciporin

KW - conformation

KW - ANTIMICROBIAL PEPTIDES

KW - PREFERRED CONFORMATION

KW - AMPULLOSPORIN

KW - TRICHOGIN GA-IV

KW - MEDIUM-LENGTH

KW - ALPHA-AMINO-ACID

KW - TOAC

KW - CHAIN-LENGTH

UR - http://www.scopus.com/inward/record.url?scp=85078172104&partnerID=8YFLogxK

U2 - 10.1002/bip.23083

DO - 10.1002/bip.23083

M3 - Article

C2 - 29127716

AN - SCOPUS:85078172104

VL - 110

JO - Peptide Science

JF - Peptide Science

SN - 2475-8817

IS - 5

M1 - e23083

ER -