Protein mimics

The well-defined helical structure associated with appropriately substituted peptoid oligomers (Section 1.6) can be employed to fashion compounds that closely mimic the stracture and function of certain bioactive peptides. There are many examples of small helical peptides (<100 residues) whose mimicry by non-natural ohgomers could potentially yield valuable therapeutic and bioactive compounds. This section describes peptoids that have been rationaUy designed as mimics of antibacterial peptides, lung surfactant proteins, and coUagen proteins. Mimics of HIV-Tat protein, although relevant to this discussion, were described previously in this chapter (Sections 1.3.2 and 1.4.1). 

Figure 28 A dendrimer-based approach for the design of globular protein mimic using glutamic (Glu) and aspartic (Asp) acids as the building blocks and adamantyl as the core [151].

PTHrP). This protein mimics the action of endogenous parathyroid hormone on bones. Local osteolytic activity causes 20% to 30% of hypercalcemia cases, although local osteolytic activity also may have a humoral component. Local production of various factors directly stimulates osteoclastic... 

Mimics based on natural enzymes Mimics based on other proteins Mimics based on other biopolymers Mimics based on synthetic macromolecules Mimics based on small-molecule host-guest interactions... 

F.A. Etzkorn, Protein mimics inhibit enzymes that regulate the cell cycle, 2004 Abstracts of papers 228th ACS National meeting, Aug. 22-26. 

Owing to their size and the feasibility of controlling the dendrimer structure and globular morphology via their synthesis, dendrimers with chiral branching scaffold are of interest as potential protein mimics. In addition, the introduction of chiral branching units or spacers into the molecular scaffold should lead to the development of non-symmetrical macromolecular conformations and provide chiral cavities for asymmetrical catalysis or chiral recognition processes. 

II. REPLACEMENT OF THE PROXIMAL HISTIDINE LIGAND IN Mb INTO CYSTEINE OR TYROSINE PROTEIN MIMICS OF CYTOCHROME... 

Diederich et al.11921 reported the divergent synthesis of dendrimers possessing porphyrin cores with the aim of modeling redox potentials of electroactive chromophores via environmental polarity modification. The dendrimers thus can be considered as electron-transfer protein mimics for such proteins as cytochrome c oxidation potentials for cytochrome c in aqueous solution are known to be 300-400 mV more positive than those reported for similarly ligated heme mimics lacking hydrophobic peptide encapsulation J193a ... 

Figure 29.32. Structure of Ribosome Release Factor (RRF). RRF is another protein that resembles tRNA. The a helices of this protein mimic the tRNA structure. In contrast, in EF-G, P strands are the mimics, revealing an independent evolutionary origin.

The HIV-protease inhibitors, probably the most successful drugs used to prevent HIV turning into AIDS, are all protein mimics with an unreactive C-C bond replacing an amide link. That bond is marked with a broad arrow in norvir 152, Bristol-Myers Squibb s entry in this class. Amide disconnection reveals that the key central part of the molecule 154 looks like a phenylalanine dipeptide except that it has the C C bond. So can we make 154 from phenylalanine 4 ... 

Chamorro C, Kniijtzer JAW, Fatsaraki M, Balzaiini J, Liskamp RMJ (2009) A general approach Jot the non-stop solid phase synthesis of TAC-scaffolded loops towards protein mimics containing discontinuous epitopes. Chem Cramram 821—823... 

Since dendrimers are often pursued as globular protein mimics, it is useful to be able to vary each monomer unit from the other, ie introduce sequences within dendrimers. For achieving such a possibility, the convergent approach is an ideal synthetic protocol. The Thayumanavan group has developed two synthetic protocols in which the peripheral functionalities of the dendrimers are all different from each other (21,22). In the first approach, we used an AB2 monomer unit in which one of the B units is protected. This approach was demonstrated by the monoprotection of one of the phenolic groups of 3,5-dihydroxybenzyl alcohol with an allyl moiety. The resultant monomer was treated with one alkylating agent to... 

The earliest synthetic pol5uneric micelles, often referred to as polysoaps, were prepared as biological protein mimics (306-308). Copol5uners synthesized... 

Dendritic Dipeptides as Aquaporin Transmembrane Protein Mimics. 188... 

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