Three‐Dimensional Organization of Helices: Design Principles for Nucleobase‐Functionalized β‐Peptides

Abstract

The construction and molecular recognition of various three-dimensional biomimetic structures is based on the predictable de novo design of artificial molecules. In this regard beta-peptides are especially interesting, since stable secondary structures are obtained already with short sequences; one of them is the 14-helix in which every third residue has the same orientation. The covalent functionalization of every third 14-helix side chain with nucleobases was used for a reversible organization of two helices based on nucleobase pairing. A series of beta-peptides with various nucleobase sequences was synthesized and the stability of double strand formation was investigated. As few as four nucleobases are sufficient for considerable duplex stability. The stability of base pairing was examined by temperature-dependent UV spectroscopy and the formation of the 14-helix was confirmed by circular dichroism (CD) spectroscopy. The preferred strand orientation of complementary-nucleobase-modified beta-peptide helices was investigated as well as the influence of helix content on the duplex stability. The preorganization of a 14-helix in regard to double-strand recognition was tuned by the sequential order of polar beta-amino acids or by the amount of 2-aminocyclohexanecarboxylic acid units incorporated, which are known to facilitate 14-helix formation, respectively.

Novel bis-phenanthridine derivatives with easily tunable linkers, study of their interactions with DNA and screening of antiproliferative activity

“…As a synthetic route to an easily variable spacer backbone, we used solid phase peptide synthesis procedures [17].The most prominent advantages of proposed approach are: a) an easy preparation of novel amino acid-phenanthridine monomer; b) oligomerisation of monomers can be easily controlled by means of order, chirality of linker, distance between monomers; c) simple and fast preparation of new generations of compounds by modification of the last (oligomerisation) step.…”

Secondary Structure Dependent Self‐Assembly of β‐Peptides into Nanosized Fibrils and Membranes

“…[9] Through observation of the packing of the secondary structural units in the solid state, tertiary structural motifs potentially available for b-peptides were identified; Xray crystallographic studies revealed a H14 helix-bundle motif [10] and a polar pleated sheet. [3] As a further step towards tertiary structures, designed b-peptide helices have been observed to exhibit self-association in solution, [11][12][13][14] but the creation of distinct tertiary structures with specific morphologies still remains a challenge.…”

Molecular architecture with carbohydrate functionalized β-peptides adopting 314-helical conformation

“…In addition, β-peptide 3 14 -helices furnish an ideal structural backbone for the well-organized presentation of recognition units since incorporation of artificial β-amino acids allows positioning of side chains on one side of the helix in equidistant 5 Å intervals. This concept was proven to be beneficial for base-pair recognition of β-peptide nucleic acids leading to high duplex stabilities of entropically preorganized recognition units [15–17]. Further, the presentation of a sugar unit on a β-peptide helical topology was reported by Arvidsson and coworkers [18–19].…”