Fine Tuning of the Cation Affinity of Artificial Receptors Based on Cyclic Peptides by Intramolecular Conformational Control

Abstract

A series of cyclic hexapeptides consisting of alternating 4-substituted 3-aminobenzoic acid units (R = CH 3 , Cl, CH 2 OCH 3 , OCH 3 , COOCH 3 ) and residues of the natural amino acid proline has been prepared and their ion affinities have been investigated. Whereas the unsubstituted parent compound (R = H) is able to bind cations through cation−π interactions with the aromatic subunits, as well as anions through hydrogen bonding with the peptide NH groups, the introduction of substituents at the 4-positions of the aromatic rings results in complete loss of the anion affinity. The cation complex stabilities depend on the substituents and cover a wide range from K a = 140 M −1 for R = CH 3 to K a = 10800 M −1 for R = COOCH 3 (K a = 1260 M −1 for R = H) with n-butyltrime-

Molecular recognition of organic ammonium ions in solution using synthetic receptors

“…164) that was able to bind ammonium ions with stability constants between 11000 and 42000 M −1 in chloroform. The series of cyclic hexapeptides contains different 4-substituted 3-aminobenzoic acid units (R = CH 3 , Cl, CH 2 OCH 3 , OCH 3 , COOCH 3 ) [746]. The authors demonstrated that cyclic peptides 233 bind a variety of ammonium iodide salts with positive co-operativity in CDCl 3 .…”

Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity

“…Finally, the protected PROTACs were deprotected using method V to yield PROTACs (1g, 1h, 1l and 1p) shown in scheme 5. The two starting materials 4-(2-methoxy-2-oxoethoxy)benzoic acid (21) [67] and benzyl 3-amino-4-chlorobenzoate (22) which were prepared as previously described [68], were reacted together using method IIIC to afford benzyl 4-chloro-3-[4-(2methoxy-2-oxoethoxy)benzamido]benzoate (23). Deprotection of the benzyl ester was achieved using method V, and the resulted acid was reacted with O- Finally, the protected HDAC ligand was reacted with E3 ligase-linker-NH 2 conjugate (53) following method IIIA to yield the protected PROTAC which was deprotected to yield PROTAC (1i) using method VII.…”

Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity

“…Finally, the protected PROTACs were deprotected using method V to yield PROTACs (1g, 1h, 1l and 1p) shown in scheme 5. The two starting materials 4-(2-methoxy-2-oxoethoxy)benzoic acid (21) [68] and benzyl 3-amino-4-chlorobenzoate (22) which were prepared as previously described [69], were reacted together using method IIIC to afford benzyl 4-chloro-3-[4-(2methoxy-2-oxoethoxy)benzamido]benzoate (23). Deprotection of the benzyl ester was achieved using method V, and the resulted acid was reacted with O- Finally, the protected HDAC ligand was reacted with E3 ligase-linker-NH 2 conjugate (53) following method IIIA to yield the protected PROTAC which was deprotected to yield PROTAC (1i) using method VII.…”