Spatially Addressed Synthesis of Amino- and Amino-Oxy-Substituted 1,3,5-Triazine Arrays on Polymeric Membranes

Abstract

Effective spatially addressed parallel assembly of trisamino- and amino-oxy-1,3,5-triazines was achieved by applying the SPOT-synthesis technique on cellulose and polypropylene membranes. In addition to developing a suitable linker strategy and employing amines and phenolate ions as building blocks, a highly effective microwave-assisted nucleophilic substitution procedure at membrane-bound monochlorotriazines was developed. The 1,3, 5-triazines obtained could be cleaved in parallel from the solid support by TFA vapor to give compounds adsorbed on the membrane surface in a conserved spatially addressed format for analysis and screening. The reaction conditions developed were employed for the synthesis of 8000 cellulose-bound 1,3,5-triazines which were probed in parallel for binding to the anti-transforming growth factor-alpha monoclonal antibody Tab2 in order to identify epitope mimics.

Controlled Microwave Heating in Modern Organic Synthesis

“…[223,224] Apart from traditional cross-linked polystyrene resins a number of different supports and formats have been used in microwave-assisted SPOS. These include tentagel resins, [117,213,214,225] cellulose membranes (SPOT synthesis), [226,227] cellulose beads, [228] and glass surfaces. [229] Janda and co-workers have described the use of JandaJel as the support in the solid-phase synthesis of oxazoles (Scheme 48).…”

Microwave Assisted Reactions in Organic Chemistry: A Review of Recent Advances

“…But, it was observed that this gradient did not affect the particular chemistry (Glass & Combs, 2001). Wenschuh et al (2000) have synthesised a library of trisamino-and amino-oxy-1,3,5-triazines with 8000-members in their study, by carrying out microwave-assisted nucleophilic substitution at cellulose-membrane-bound monochlorotriazines. Microwave assisted substitution of the chlorine atom in monochlorotriazines is the major step in this reaction.…”

Exploring Biochemistry and Cellular Biology with Protein Libraries

“…This technique features chemical synthesis at defined "spots" on a solid support, such as cellulose (e.g., filter paper). Polypropylene membranes have also been used to increase the chemical and mechanical stability between the attached molecule and the membrane (Scharn et al, 2000). For example, for SPOT synthesis of peptide libraries, the activated amino acids are dotted at specific positions onto a functionalized membrane forming a "spot" within which miniscale coupling reactions can proceed.…”

“…Conventional solid phase peptide synthesis proceeds with each additional amino acids added directly to the defined spots. Linkers can also be included on the functionalized membrane to allow cleavage and recovery of the synthesized product Scharn et al, 2000). This method has been employed for a number of applications ranging from the identification of proteinprotein interactions, development of protein mimics (Bracci et al, 2001), optimization of peptide spotting densities, improved reproducibility, increased signal intensities (Kramer et al, 1999) and enzyme-substrate recognition (Reineke et al, 2001).…”