1.Synthesis of peptides mediated by KOBt.
Sivanandaiah KM;Babu VV;Shankaramma SC Int J Pept Protein Res. 1994 Jul;44(1):24-30.
Coupling of Fmoc-amino acid chlorides can be mediated by the potassium salt of 1-hydroxybenzotriazole (KOBt), the reaction being carried out in an organic medium. The use of a base like NaHCO3/Na2CO3 or DIEA/NMM/pyridine is not necessary. Coupling is fast and racemization free; the work-up, isolation of the product and scale-up are easy. The pentapeptide sequence of Fmoc-[Leu]enkephalin was thus synthesized in the solution phase on a 5 mmol scale without isolation of any intermediate. Acylation of C-protected N-methylamino acid esters by Fmoc-N-methylamino acid chlorides by this procedure is also feasible, as demonstrated by the synthesis of cyclosporin A fragments 4-7 and 8-11. The peptides obtained in high yields were crystalline solids, unlike earlier reports in which they were obtained mostly as oily or foamy intermediates. They showed spectral properties identical with those of the authentic compounds.
2.O MAS NMR Correlation Spectroscopy at High Magnetic Fields.
Keeler EG;Michaelis VK;Colvin MT;Hung I;Gor'kov PL;Cross TA;Gan Z;Griffin RG J Am Chem Soc. 2017 Dec 13;139(49):17953-17963. doi: 10.1021/jacs.7b08989. Epub 2017 Nov 30.
The structure of two protected amino acids, FMOC-l-leucine and FMOC-l-valine, and a dipeptide, N-acetyl-l-valyl-l-leucine (N-Ac-VL), were studied via one- and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy. Utilizing ;17;O magic-angle spinning (MAS) NMR at multiple magnetic fields (17.6-35.2 T/750-1500 MHz for ;1;H) the ;17;O quadrupolar and chemical shift parameters were determined for the two oxygen sites of each FMOC-protected amino acids and the three distinct oxygen environments of the dipeptide. The one- and two-dimensional, ;17;O, ;15;N-;17;O, ;13;C-;17;O, and ;1;H-;17;O double-resonance correlation experiments performed on the uniformly ;13;C,;15;N and 70% ;17;O-labeled dipeptide prove the attainability of ;17;O as a probe for structure studies of biological systems. ;15;N-;17;O and ;13;C-;17;O distances were measured via one-dimensional REAPDOR and ZF-TEDOR experimental buildup curves and determined to be within 15% of previously reported distances, thus demonstrating the use of ;17;O NMR to quantitate interatomic distances in a fully labeled dipeptide. Through-space hydrogen bonding of N-Ac-VL was investigated by a two-dimensional ;1;H-detected ;17;O R;3;-R-INEPT experiment, furthering the importance of ;17;O for studies of structure in biomolecular solids.
3.FMOC-amino acid surfactants: discovery, characterization and chiroptical spectroscopy.
Vijay R;Polavarapu PL J Phys Chem A. 2012 Nov 8;116(44):10759-69. doi: 10.1021/jp308134m. Epub 2012 Oct 25.
The sodium salts of amino acids with hydrophobic fluorenyl methyloxy carbonyl (FMOC) group and short alkyl side chains are found to have surfactant properties. This was ascertained first through visual observation of concentration dependent solution behavior and then confirmed by tensiometry measurements. The critical micelle concentrations (CMCs) for the sodium salts of FMOC-l-valine, FMOC-L-leucine, and FMOC-L-isoleucine have been determined to be ~0.1 M. The sodium salt of FMOC-l-norleucine forms a gel at >0.2 M. Powder X-ray diffraction measurements indicated that these surfactants adopt bilayer structures. Three different chiroptical spectroscopic properties, namely optical rotation, electronic circular dichroism, and vibrational circular dichroism, are presented for these surfactants. The specific rotation is found to exhibit an unprecedented increase with concentration beyond CMC. This observation opens up a new area of research relating the concentration dependent increase in specific rotation to the size and shape of aggregates formed by the surfactants.
