Details

Autor(en) / Beteiligte

• Kang, Sang-Woo
• Gothard, Chris M
• Maitra, Santanu
• Atia-tul-Wahab
• Nowick, James S

Titel

A New Class of Macrocyclic Receptors from iota -Peptides

Ist Teil von

• Journal of the American Chemical Society, 2007-02, Vol.129 (6), p.1486-1487

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• This paper presents a new class of macrocycles and demonstrates the potential of these macrocycles to bind guests and to display different substituents in sequence. The macrocyclic iota-peptides (ι-peptides) 1 are based on the ι-amino acid aminodiphenylmethanecarboxylic acid (Adc). Adc can be thought of as an analogue of the α-amino acid glycine that has been enlarged fourfold, to 1.0 nm in length, by insertion of two benzene rings into the main-chain bonds. The Fmoc-protected Adc variants 2 are readily prepared in good yields on a multigram scale, and can be used to prepare macrocyclic ι-peptides 1 by solid-phase synthesis of protected linear Adc tetramers on 2-chlorotrityl resin, followed by macrocylization, deprotection, and RP-HPLC purification. The 1H NMR spectrum of cyclo(AdcK)4 (1b) in DMSO-d 6 solution shows only one set of resonances, which arise from a “square” conformer with fourfold symmetry and all trans-amide linkages; the spectrum in D2O shows resonances associated with both the “square” conformer and a “rectangular” conformer with twofold symmetry comprising alternating cis- and trans-amide linkages. 1H NMR experiments show that cyclo(AdcK)4 forms a 1:1 complex with sodium cholate, with an association constant of ca. 10 000 M-1 in D2O solution. Molecular modeling studies show that the cavity of the “square” conformer is complementary in size to sodium cholate and suggest that the ring is slightly strained. Isomeric macrocycles cyclo(AdcKYAdcKAAdcKTAdcKV) (1c) and cyclo(AdcKYAdcKT AdcKVAdcKA) (1d) were synthesized to demonstrate the ability of the macrocyclic ι-peptides to achieve sequence and diversity.