D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides

被引：6

作者：

Humpola, Maria Veronica ^{[1
]}

Spinelli, Roque ^{[1
,2
]}

Erben, Melina ^{[1
]}

Perdomo, Virginia ^{[2
,3
]}

Tonarelli, Georgina Guadalupe ^{[1
]}

Albericio, Fernando ^{[4
,5
]}

Siano, Alvaro Sebastian ^{[1
,2
]}

机构：

[1] Univ Nacl Litoral, Fac Bioquim & Ciencias Biol, Dept Quim Organ, Lab Peptidos Bioact, S3000ZAA, Santa Fe, Argentina

[2] Consejo Nacl Invest Cient & Tecn CONICET, C1425FQB, Buenos Aires, Argentina

[3] Univ Nacl Rosario, Fac Ciencias Bioquim & Farmaceut, Area Parasitol, S2002KTT, Rosario, Argentina

[4] Univ KwaZulu Natal, Sch Chem & Phys, ZA-4001 Durban, South Africa

[5] Univ Barcelona, Networking Ctr Bioengn Biomat & Nanomed, Consorcio Ctr Invest Biomed Red Bioingn Biomat &, Dept Organ Chem, Barcelona 08028, Spain

来源：

ANTIBIOTICS-BASEL | 2023年 / 12卷 / 05期

关键词：

antimicrobial peptides; N-methyl amino acids; D-amino acids; enzymatic stability; toxicity; OMIGANAN PENTAHYDROCHLORIDE; SECONDARY STRUCTURE; STABILITY; HYDROPHOBICITY; ANALOGS; DESIGN; MODEL;

D O I：

10.3390/antibiotics12050821

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic a-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation. The study provides insights into the design and optimization of antimicrobial peptides to achieve improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies.

引用

页数：15

共 45 条

[1] STRUCTURAL STUDIES OF A FAMILY OF HIGH-AFFINITY LIGANDS FOR GPIIB/IIIA [J].