title: A double catgrip mixed L and D mini protein only 20 residues long.
abstract: 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 beta-hairpins as bracelet and boat shaped molecules. Illustrating the prospect for functional design, a 20-residue four-stranded mini-beta protein is now customized stereochemically as a canoe shaped molecule. A conformational construct of four side by side hydrogen-bonded strands in alternately (l)beta, (d)beta conformation, joined via Type-II/II' beta-turns, is planned to be preponderantly apolar in beta-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.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India.
authors.forename: Soumendra
authors.initials: S
authors.lastname: Rana
authors.forename: Bijoy
authors.initials: B
authors.lastname: Kundu
authors.forename: Susheel
authors.initials: S
authors.lastname: Durani
mesh_terms: D000595:Amino Acid Sequence; D015195:Drug Design; D006860:Hydrogen Bonding; D013058:Mass Spectrometry; D008672:Metals, Alkali / Q000737:chemistry*; D008673:Metals, Alkaline Earth / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D008672:Metals, Alkali; D008673:Metals, Alkaline Earth; D010455:Peptides; D011506:Proteins