Two-step fluorescence screening of CD21-binding peptides with one-bead one-compound library and investigation of binding properties of N-(2-hydroxypropyl)methacrylamide copolymer-peptide conjugates

被引：22

作者：

Ding, Hui

Prodinger, Wolfgang M.

Kopecek, Jindrich ^{[1
]}

机构：

[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA

[2] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA

[3] Innsbruck Med Univ, Dept Hyg Microbiol & Social Med, Innsbruck, Austria

来源：

BIOMACROMOLECULES | 2006年 / 7卷 / 11期

关键词：

D O I：

10.1021/bm060508f

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Using the one-bead one-compound (OBOC) combinatorial method, four heptapeptide ligands of CD21 receptor, a cell surface marker of malignant B cell lymphoma, were identified with an innovative two-step fluorescence screening method to overcome the limitation caused by autofluorescence of TentaGel resin. The binding affinities of selected peptides, YILIHRN (B1), PTLDPLP (B2), and LVLLTRE (B3), were in the micromolar region as determined by a fluorescence quenching assay. Peptide B1 was conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via spacers of different lengths, composed of one to four repeats of the 8-amino-3,6-dioxaoctanoic acid (A) group. The evaluation of the biorecognizability of HPMA copolymer-B1 conjugates by the CD21 receptor revealed that increasing the number of repeats of A in the spacer from one to three resulted in continuous improvements in the biorecognition by the CD21 receptor; the increase from three to four repeats showed no significant effect. This work showed the potential of the OBOC combinatorial approach to select peptide ligands as targeting moieties for CD21 specific polymeric drug carriers.

引用

页码：3037 / 3046

页数：10

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