Stereoselective Recognition of Tripeptides Guided by Encoded Library Screening:  Construction of Chiral Macrocyclic Tetraamide Ruthenium Receptor for Peptide Sensing

Abstract

[structure: see text] Molecule sensor 1 is devised by incorporating the reporting unit of ruthenium(II) complex and two recognition motifs of chiral cyclotetraamides on the sidearms. The target binding tripeptides for sensor 1 were readily identified by using an encoded library screening method. This solid-phase screening indicated a preferable binding of molecule 1 with d-alanine over the l-isomer. The optical and NMR studies for the binding events of 1 with tripeptides Ac-Ala-Gly-Ala-NHC(12)H(25) in the solution phase showed a consistent trend for the stereoselective recognition of the dd-isomer over the ld-, dl-, and ll-isomers.

Specific Electrostatic Molecular Recognition in Water

“…Poly[acryloyl‐bis (aminopropyl)polyethylene glycol] (PEGA) resin was selected as the solid support because of its low background fluorescence and absence of unspecific interactions with reagents, peptides, and proteins. Moreover, PEGA shows excellent swelling properties in polar solvents and is generally biocompatible …”

“…Moreover,P EGA shows excellent swelling properties in polar solvents and is generally biocompatible. [23][24][25] Prior to library assembly, the target was modelled in Molecular Operating Environment (MOE)a nd virtually screened for possible recognition elements. We analyzed substitution patterns showing potentiali nteractions with the selected target peptide,u sing an octapeptide structure to generatel igands with increased probability of strong and specific interactions.…”

“…[16][17][18] In these examples, recognition is of the lock-and-key type, which differs significantly from the induced fit of designed synthetic peptide-receptor pairs. [19][20][21] Artificial receptors developed through combinatorial screening showb inding constantsi nt he range 10 À5 -10 À3 m, and include examples such as tweezer-and tripodal peptides, [22] bicyclic peptide receptors, [23] and peptidomimetic receptors binding to aR as-protein. Interestingly,M aeda et al reported the identification of pentapeptides binding to a dopamine D2 receptor fragment with K d values of 10 À5 m by using acombinatorialb ead-bead interaction assay.…”

“…In these examples, recognition is of the lock‐and‐key type, which differs significantly from the induced fit of designed synthetic peptide–receptor pairs . Artificial receptors developed through combinatorial screening show binding constants in the range 10 −5 –10 −3 m , and include examples such as tweezer‐ and tripodal peptides, bicyclic peptide receptors, and peptidomimetic receptors binding to a Ras‐protein. Interestingly, Maeda et al.…”

Copper(I)‐Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β‐Tetrapeptide Analogues

“…The crude residue was purified by column chromatography on silica gel by using 10 %e thyl acetate in hexane as as olvent system to affordt he desired product (23)a sacolorless liquid (2005 mg, 84 %). 1 [48] A1n solution of NaOH (10 mL) was added to as tirred solution of 22 (1500 mg, 5.76 mmol) in methanol (20 mL), and the resultant mixture was stirred for 8h at RT under an itrogen atmosphere. After completion of the reaction, as monitored by TLC, the reaction was concentrated under reduced pressure to remove methanol, and then extracted with DCM (30 mL).…”