Substitution of the GalNAc-α-O-Thr11 residue in drosocin with O-linked glyco-peptoid residue: Effect on antibacterial activity and conformational change

被引：12

作者：

Ahn, Mija ^{[3
]}

Murugan, Ravichandran N. ^{[3
]}

Nan, Yong Hai ^{[1
,2
]}

Cheong, Chaejoon ^{[3
]}

Sohn, Holk ^{[4
]}

Kim, Eun-Hee ^{[3
]}

Hwang, Eunha ^{[3
]}

Ryu, Eun Kyoung ^{[3
]}

Kang, Shin Won ^{[5
]}

Shin, Song Yub ^{[1
,2
]}

Bang, Jeong Kyu ^{[3
]}

机构：

[1] Chosun Univ, Dept Biomat, Grad Sch, Kwangju 501759, South Korea

[2] Chosun Univ, Sch Med, Dept Cellular & Mol Med, Kwangju 501759, South Korea

[3] Korea Basic Sci Inst, Div Magnet Resonance, Ochang 363883, Chung Buk, South Korea

[4] Univ Texas Austin, Coll Nat Sci, Dept Chem & Biochem, Austin, TX 78712 USA

[5] Pusan Natl Univ, Dept Chem, Pusan 609735, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 20期

关键词：

Glyco-peptoid; Antibacterial peptide; Drosocin; Structure-activity relationship (SAR); PEPTIDE; DROSOPHILA; ANALOGS; NMR;

D O I：

10.1016/j.bmcl.2011.08.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

One of the obvious disadvantages of natural peptides is their liability to proteases. Among the several solutions for this issue, peptoids or oligomers of N-substituted glycine have emerged as a promising tool that may enhance the stability of proteolysis-susceptible natural peptides. We have synthesized the drosocin and its glyco-peptoid analogues linked O-GalNAc at the Thr(11) residue. One of our glyco-peptoid analogues showed an increased antibacterial activity by the modification of the Thr(11) residue with glycopeptoid. Structure-activity relationship studies revealed that the antibacterial activity by glyco-peptoid drosocin requires three key elements: free hydroxyl group on the carbohydrate moiety, gamma-methyl group of the Thr(11) residue derivative and (S)-configuration over (R)-configuration. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：6148 / 6153

页数：6

共 13 条

[1] Enlarged scale chemical synthesis and range of activity of drosocin, an O-glycosylated antibacterial peptide of Drosophila [J].

Bulet, P ;

Urge, L ;

Ohresser, S ;

Hetru, C ;

Otvos, L .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1996, 238 (01) :64-69

[2]

BULET P, 2000, EUR J BIOCHEM, V40, P3016

[3] Biological evaluation of Tyr6 and Ser7 modified drosocin analogues [J].

de Visser, PC ;

van Hooft, PAV ;

de Vries, AM ;

de Jong, A ;

van der Marel, GA ;

Overkleeft, HS ;

Noort, D .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (11) :2902-2905

[4] Antimicrobial peptides: Synthesis and antibacterial activity of linear and cyclic drosocin and apidaecin 1b analogues [J].

Gobbo, M ;

Biondi, L ;

Filira, F ;

Gennaro, R ;

Benincasa, M ;

Scolaro, B ;

Rocchi, R .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (20) :4494-4504

[5] Antifreeze glycopeptide analogues: microwave-enhanced synthesis and functional studies [J].

Heggemann, Carolin ;

Budke, Carsten ;

Schomburg, Benjamin ;

Majer, Zsuzsa ;

Wissbrock, Marco ;

Koop, Thomas ;

Sewald, Norbert .

AMINO ACIDS, 2010, 38 (01) :213-222

[6] THE HUMORAL ANTIBACTERIAL RESPONSE OF DROSOPHILA [J].

HOFFMANN, JA ;

HETRU, C ;

REICHHART, JM .

FEBS LETTERS, 1993, 325 (1-2) :63-66

[7] Design of a functionally equivalent nonglycosylated analog of the glycopeptide antibiotic formaecin I [J].

Kaur, Kanwal J. ;

Pandey, Shashank ;

Salunke, Dinakar M. .

PROTEIN SCIENCE, 2007, 16 (02) :309-315

[8] Oncocin (VDKPPYLPRPRPPRRIYNR-NH2): A Novel Antibacterial Peptide Optimized against Gram-Negative Human Pathogens [J].

Knappe, Daniel ;

Piantavigna, Stefania ;

Hansen, Anne ;

Mechler, Adam ;

Binas, Annegret ;

Nolte, Oliver ;

Martin, Lisandra L. ;

Hoffmann, Ralf .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (14) :5240-5247

[9] ULTRASENSITIVE ASSAYS FOR ENDOGENOUS ANTIMICROBIAL POLYPEPTIDES [J].

LEHRER, RI ;

ROSENMAN, M ;

HARWIG, SSSL ;

JACKSON, R ;

EISENHAUER, P .

JOURNAL OF IMMUNOLOGICAL METHODS, 1991, 137 (02) :167-173

[10]

Longenecker B. M., 1993, VACCINE RES, V2, P151

← 1 2 →