A novel GIP analogue, ZP4165, enhances glucagon-like peptide-1-induced body weight loss and improves glycaemic control in rodents.

Aim: To investigate the effects of the novel glucose-dependent insulinotropic polypeptide (GIP) analogue, ZP4165, on body weight and glycaemic control in rodents, and to investigate if ZP4165 modulates the anti-obesity and anti-hyperglycaemic effects of a glucagon-like peptide-1 (GLP-1) agonist (liraglutide).

Methods: The acute insulinotropic effect of ZP4165 was investigated in rats during an oral glucose tolerance test. The long-term effects of ZP4165 on body weight and glycaemic control, either alone or in combination with liraglutide, were assessed in diet-induced obese mice and diabetic db/db mice.

Backbone amide linker strategy: protocols for the synthesis of C-terminal peptide aldehydes.

In the backbone amide linker (BAL) strategy, the peptide is anchored not at the C-terminus but through a backbone amide, which leaves the C-terminal available for various modifications. This is thus a very general strategy for the introduction of C-terminal modifications. The BAL strategy was originally developed using a trisalkoxybenzyl linker, but since then range linkers (handles) with different properties have also been developed.

Synthesis of C-terminal peptide thioesters using Fmoc-based solid-phase peptide chemistry.

This chapter provides two protocols for the solid-phase synthesis of peptide thioesters using N (α) -Fmoc-protected amino acids. The first protocol is based on a so-called safety-catch linker, while the second relies on a backbone amide linker.

Linkers, resins, and general procedures for solid-phase peptide synthesis.

This chapter describes the basic protocols for solid-phase peptide synthesis using the Fmoc group as the N (α)-protecting group (Fmoc-SPPS). The chapter introduces resins and their handling, choice of linkers, and the most common methods for peptide chain assembly. The proper choice of resins and linkers for solid-phase synthesis is a key parameter for successful peptide synthesis.

3- Instead of 4-helix formation in a de novo designed protein in solution revealed by small-angle X-ray scattering.

De novo design and chemical synthesis of proteins and their mimics are central approaches for understanding protein folding and accessing proteins with novel functions. We have previously described carbohydrates as templates for the assembly of artificial proteins, so-called carboproteins. Here, we describe the preparation and structural studies of three alpha-helical bundle carboproteins, which were assembled from three different carbohydrate templates and one amphiphilic hexadecapeptide sequence.