title: 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.
abstract: 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.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, and Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Prodinger
authors.forename: Jindrich
authors.initials: J
authors.lastname: Kopecek
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000178:Acrylamides; D005456:Fluorescent Dyes; D010455:Peptides; D017464:Receptors, Complement 3d; C032976:N-(2-hydroxypropyl)methacrylamide