1. Extensively stereodiversified scaffolds for use in diversity-oriented library synthesis
Tiffany Malinky Gierasch, Zhangjie Shi, Gregory L Verdine Org Lett. 2003 Mar 6;5(5):621-4. doi: 10.1021/ol027116f.
The syntheses of stereodiverse libraries of 12 and 19 are reported, where each asterisk represents an independently varied stereocenter. These scaffolds provide additional templates for investigations of geometric diversity in library syntheses. Libraries of these N-Fmoc-amino acids were further functionalized by incorporation into a peptide sequence, demonstrating the utility of 12 and 19 as building blocks for diversity oriented synthesis.
2. Synthesis of the very acid-sensitive Fmoc-Cys(Mmt)-OH and its application in solid-phase peptide synthesis
K Barlos, D Gatos, O Hatzi, N Koch, S Koutsogianni Int J Pept Protein Res. 1996 Mar;47(3):148-53. doi: 10.1111/j.1399-3011.1996.tb01338.x.
S-4-methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc-Cys(Mmt)-OH by its reaction with Fmoc-OSu. As compared to the corresponding Fmoc-Cys(Trt)-OH, the S-Mmt-function was found to be considerably more acid labile. Quantitative S-Mmt-removal occurs selectively in the presence of groups of the tert butyl type and S-Trt by treatment with 0.5-1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr1-somatostatin on 2-chlorotrityl resin. In this synthesis groups of the Trt-type were exclusively used for amino acid side-chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM-TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions.
3. Large-pore polydimethylacrylamide resin for solid-phase peptide synthesis: applications in Fmoc chemistry
J T Sparrow, N G Knieb-Cordonier, N U Obeyseskere, J S McMurray Pept Res. 1996 Nov-Dec;9(6):297-304.
We have synthesized a hydrophilic crosslinked aminoalkyl polydimethylacrylamide-beaded support upon which peptides have been assembled using standard Fmoc chemistry in automated batch-wise equipment. The resin was prepared by the free radical-initiated co-polymerization of N,N-dimethylacryl-amide, N,N'-bisacrylyl-1,3-diaminopropane and a functional monomer N-methacrylyl-1,3-diaminopropane hydrochlorid. After coupling of N-alpha-tert-butyloxycarbonyl-glycine (Boc-glycine), amino acid analyses gave resin loading capacities of 0.66 mmol/g. The resulting polymer was highly swollen by polar solvents including aqueous buffers and had an exclusion limit of 50 kDa for soluble proteins. This resin was found to be an excellent support for peptide synthesis using Fmoc chemistry. Typical purities of crude peptides were 80%-95%, including sequences that failed on conventional polystyrene resins.
