Friendly Strategy to Prepare Encoded One Bead-One Compound Cyclic Peptide Library

被引：11

作者：

Giudicessi, Silvana L. ^{[1
,2
]}

Gurevich-Messina, Luan M. ^{[1
]}

Martinez-Ceron, Maria C. ^{[1
,2
]}

Erra-Balsells, Rosa ^{[2
,3
]}

Abericio, Fernando ^{[4
,5
,6
,7
]}

Cascone, Osvaldo ^{[1
,2
]}

Camperi, Silvia A. ^{[1
,2
]}

机构：

[1] Univ Buenos Aires, Sch Pharm & Biochem, Cathedra Ind Microbiol & Biotechnol, RA-1113 Buenos Aires, DF, Argentina

[2] Consejo Nacl Invest Cient & Tecn, Natl Sci & Technol Res Council, RA-1033 Buenos Aires, DF, Argentina

[3] Univ Buenos Aires, Sch Exact & Nat Sci, Dept Organ Chem, CIHDECAR CONICET, RA-1428 Buenos Aires, DF, Argentina

[4] Inst Res Biomed, Barcelona 08028, Spain

[5] Univ Barcelona, Dept Organ Chem, E-08028 Barcelona, Spain

[6] Networking Ctr Bioengn Biomat & Nanomed, CIBER BBN, Barcelona 08028, Spain

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

来源：

ACS COMBINATORIAL SCIENCE | 2013年 / 15卷 / 10期

关键词：

combinatorial chemistry; MALDI-TOF MS/MS; peptide sequencing; affinity; solid phase; ChemMatrix resin; 2-phenylisopropyl; 4-hydroxymethylbenzoic acid; solid-phase synthesis; SOLID-PHASE SYNTHESIS; COMBINATORIAL LIBRARIES; SEQUENCE DETERMINATION; MASS-SPECTROMETRY; PROTECTING GROUP; CONVENIENT; CHEMISTRY; CLEAVAGE; LIGANDS; SUPPORT;

D O I：

10.1021/co400039a

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

One bead-one peptide libraries allow the screening of suitable ligands for any target protein. Short cyclic peptides are ideal ligands for affinity chromatography because of their high affinity and selectivity for the target protein and stability against proteases. We designed a library synthesis strategy to facilitate the identification of cyclic peptides by MS consisting of (a) sequential incorporation of a mixture of Fmoc-Ala-OH and Fmoc-Asp[2-phenylisopropyl (OPp)]-OH (15:85) to Gly-oxymethylbenzamide-ChemMatrix (Gly-HMBA-CM) resin, (b) synthesis of the combinatorial library on the resin by the divide-couple-recombine method, (c) removal of OPp with 4% TFA, (d) peptide cyclization on solid phase through side-chain Asp and amino terminus, and (e) removal of side chain protecting groups with a 95% TFA cocktail. Peptides were cleaved from the beads with ammonia and the linear code was sequenced by MALDI-TOF MS/MS. The high capacity of ChemMatrix resin together with the sensitivity of MS allows code sequencing from a single bead.

引用

页码：525 / 529

页数：5

共 29 条

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