title: Partial alloc-deprotection approach for ladder synthesis of "one-bead one-compound" combinatorial libraries.
abstract: The topologically segregated bilayer-bead concept has been applied to encoded "one-bead one-compound"(OBOC) combinatorial libraries to avoid the interference of coding tags with biological screening. In this paper, we report on the development of a novel partial Alloc-deprotection (PAD) approach and the use of this approach to establish a new ladder-synthesis method for OBOC combinatorial libraries to further exploit the concept. In the PAD approach, Alloc-protected beads are partially deprotected, sequentially layer by layer, starting from the outer layer toward the bead interior. The degree of deprotection (or thickness of each layer) is controlled by the time of exposure to the deprotecting agent, palladium. By repetitive use of the PAD approach, a small portion of Alloc-protected N termini in the bead interior is liberated in each synthetic cycle for generation of an additional ladder member such that each library bead will carry a full-length library compound on the bead surface and a series of truncated ladder members in the bead interior. For the libraries containing isobaric residues, a simple encoding strategy is introduced in the ladder-synthesis method so that the isobaric residues can be differentiated by the coding tags. One advantage of this encoding strategy is that the coding tags are confined together with the truncated ladder members in the bead interior, thus maintaining the arrangement that only the library compounds are displayed on the bead surface. The PAD approach of forming multiple concentric functional layers inside a bead is simple, reliable, and may have other applications in addition to OBOC combinatorial library bead encoding, such as the development of novel optically encoded beads for multiplex immunodiagnostics or even information recording.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, UC Davis Medical Center, 4501 X Street, Sacramento, California 95817, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Liu
authors.forename: Sukhjinder S
authors.initials: SS
authors.lastname: Gill
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000295:instrumentation / Q000379:methods*; D008863:Microspheres; D019151:Peptide Library; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000596:Amino Acids; D019151:Peptide Library