Lapses, infidelities, and creative adaptations: lessons from evaluation of a participatory market development approach in the Andes.

Participatory approaches are frequently recommended for international development programs, but few have been evaluated. From 2007 to 2010 the Andean Change Alliance evaluated an agricultural research and development approach known as the "Participatory Market Chain Approach" (PMCA). Based on a study of four cases, this paper examines the fidelity of implementation, the factors that influenced implementation and results, and the PMCA change model. We identify three types of deviation from the intervention protocol (lapses, creative adaptations, and true infidelities) and five groups of variables that influenced PMCA implementation and results (attributes of the macro context, the market chain, the key actors, rules in use, and the capacity development strategy). There was insufficient information to test the validity of the PMCA change model, but results were greatest where the PMCA was implemented with highest fidelity. Our analysis suggests that the single most critical component of the PMCA is engagement of market agents - not just farmers - throughout the exercise. We present four lessons for planning and evaluating participatory approaches related to the use of action and change models, the importance of monitoring implementation fidelity, the limits of baseline survey data for outcome evaluation, and the importance of capacity development for implementers.

Cyclic tetrapeptides via the ring contraction strategy: chemical techniques useful for their identification.

Cyclic tetrapeptides are a class of natural products that have been shown to have broad ranging biological activities and good pharmacokinetic properties. In order to synthesise these highly strained compounds a ring contraction strategy had previously been reported. This strategy was further optimised and a suite of techniques, including the Edman degradation and mass spectrometry/mass spectrometry, were developed to enable characterisation of cyclic tetrapeptide isomers. An NMR solution structure of a cyclic tetrapeptide was also generated. To illustrate the success of this strategy a library of cyclic tetrapeptides was synthesised.

A convenient method for synthesis of cyclic peptide libraries.

Cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. Owing to the robustness of amide bond chemistry, the ability to explore extensive chemical diversity by incorporation of unnatural and natural amino acids, and the ability to explore conformational diversity, through the incorporation of various constraints, arrays of cyclic peptides can be tailored to broadly sample chemical diversity. We describe the combination of a safety catch linker with a directed-sorted procedure for the synthesis of large arrays of diverse cyclic peptides for high-throughput screening.

A versatile synthetic approach to peptidyl privileged structures using a "safety-catch" linker.

Peptidyl privileged structures have been widely used by many groups to discover biologically active molecules. In this context, privileged substructures are used as "hydrophobic anchors", to which peptide functionality is appended to gain specificity. Utilization of this concept has led to the discovery of many different active compounds at a wide range of biological receptors. A synthetic approach to these compounds has been developed on a "safety-catch" linker that allows rapid preparation of large libraries of these molecules. Importantly, amide bond formation/cleavage through treatment with amines is the final step; it is a linker strategy that allows significant diversification to be easily incorporated, and it only requires the inclusion of an amide bond. In addition, chemistry has been developed that permits the urea moiety to be inserted at the N-terminus of the peptide, allowing the same set of amines (either privileged substructures or amino acid analogues) to be used at both the N- and C-termini of the molecule. To show the robustness of this approach, a small library of peptidyl privileged structures were synthesized, illustrating that large combinatorial libraries can be synthesized using these technologies.

Evaluating capacity development: Experiences from Research and Development Organizations around the World

This book explains how the project used an action-learning approach, bringing together people from various countries and different types of organizations. As they conducted six evaluation studies over the course of 3 years, project participants learned a great deal about capacity development and the process of evaluation. The authors use examples and lessons drawn from the evaluation studies as a basis for making more general conclusions regarding how capacity-development efforts and evaluation can help organizations to achieve their missions. (Au)

Difficult macrocyclizations: new strategies for synthesizing highly strained cyclic tetrapeptides.

[reaction: see text] Cyclic tetrapeptides are an intriguing class of natural products. To synthesize highly strained cyclic tetrapeptides we developed a macrocyclization strategy that involves the inclusion of 2-hydroxy-6-nitrobenzyl (HnB) group at the N-terminus and in the "middle" of the sequence. The N-terminal auxiliary performs a ring closure/ring contraction role, and the backbone auxiliary promotes cis amide bonds to facilitate the otherwise difficult ring contraction. Following this route, the all-L cyclic tetrapeptide cyclo-[Tyr-Arg-Phe-Ala] was successfully prepared.

Exploring privileged structures: the combinatorial synthesis of cyclic peptides.

Head-to-tail cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. They may therefore be considered to be privileged structures. This review outlines the strategies by which both macrocyclic cyclic peptides and cyclic dipeptides or diketopiperazines have been synthesised in combinatorial libraries. It also briefly outlines some of the biological applications of these molecules, thereby justifying their inclusion as privileged structures.

Exploring privileged structures: the combinatorial synthesis of cyclic peptides.

Head-to-tail cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. They may therefore be considered to be privileged structures. This review outlines the strategies by which both macrocyclic cyclic peptides and cyclic dipeptides or diketopiperazines have been synthesised in combinatorial libraries. It also briefly outlines some of the biological applications of these molecules, thereby justifying their inclusion as privileged structures.