M. Baumann et al., Combinatorial synthesis of cholesterol ester transfer protein-mRNA ligandsand screening by nondenaturating gel-electrophoresis, J MED CHEM, 44(13), 2001, pp. 2172-2177
RNA, as one of the biomolecules with the most structural and functional div
ersity, is an attractive therapeutic target.(1) Employing combinatorial che
mistry methods, small peptide ligands were found, which bind to a short RNA
with important biological functions. A 23-nt RNA oligonucleotide from the
cholesterol ester transfer protein mRNA was chosen as a molecular target.(2
) A 27-nt RNA oligonucleotide from the human immunodeficiency virus type-1
(HN-1) TAR RNA was used to control the binding specificity.(3) Tetrapeptide
libraries, composed of the amino acids Lys, Tyr, Leu, lie, and Arg, with a
nd without C- and N-terminal lysines, were synthesized by a combination of
combinatorial and divergent solid-phase synthesis. Gel-shift affinity scree
ning was used to extract the peptides with the best RNA binding properties.
The peptide Lys-Tyr-Lys-Leu-Tyr-Lys-Cys-NH2 (1) showing micromolar affinit
y to its RNA target was characterized with circular dichroism (CD), ultra v
iolet (UV) measurement, and H-1 NMR spectroscopy.