A double catgrip mixed l and d mini protein only 20 residues long

Stereochemistry limits but also defines proteins, as conformational constructs stereospecific for poly-l structure. Employed as a variable in sequence, stereochemistry could make proteins customizable in the letters of l and d amino acid alphabet. In proof of concept, we previously demonstrated stereochemical reengineering of canonical β-hairpins as bracelet and boat shaped molecules. Illustrating the prospect for functional design, a 20-residue four-stranded mini-β protein is now customized stereochemically as a canoe shaped molecule. A conformational construct of four side by side hydrogen-bonded strands in alternately lβ, dβ conformation, joined via Type-II/II′ β-turns, is planned to be preponderantly apolar in β-sheet favoring residues, interspersing two ion pairs, and suitably l and d in sequence. Synthesis followed by MD, NMR, CD, and MALDI-MS studies established the molecule as a canoe shaped fold in water, demonstrable in affinity of alkali and alkaline-earth metal ions as expected given its catgrip like elements. Another success in accomplishing a synthetic miniprotein complex in stereochemistry and stereospecific in conformation, exceptionally small yet functional in metal ion affinity, affirms the value in combined l and d alphabet in programming molecular shapes and functions stereochemically.

Proteins stereochemically customizable in form and function.Figure optionsDownload as PowerPoint slide