Peptides lipid-like

Acid- and base-sensitive lipidated peptides can be selectively deprotected by enzymatic hydrolysis of choline esters.[13al Choline esters of simple peptides, but also of sensitive peptide conjugates like phos-phorylated and glycosylated peptides,1141 nucleopep-tides1151 and lipidated peptides,113,1631 can be cleaved with acetyl choline esterase (AChE) and butyryl choline esterase (BChE) under virtually neutral conditions with complete chemoselectivity. Acid-labile farnesyl groups and base-sensitive thioesters are not attacked. 

In Scheme 26 a selection of lipidated peptide sequences synthesized via this approach is shown. A variety of N- and H-Ras-derived peptide sequences was obtained bearing different types of lipids like farnesyl, palmitoyl, and geranylgeranyl and a fluorescent-labeled geranyl group. Furthermore, fluorescent markers like nitroben-zoxadiazole and photoactivatable groups were introduced. 

In order to achieve thorough fundamental understanding of bio molecular self-assembly, it is imperative to study ID tape-like self-assembly not only in bulk solution but also at interfaces. An example of a biologically relevant interface is that of the lipid bilayer. Systematic peptide-lipid studies have begun to offer an insight into the basic principles and mechanisms of interactions of selfassembling peptides with model lipid layers (Protopapa et al., 2006). 

G-protein coupled receptors constitute the largest family of signal transduction membrane proteins. They mediate responses of many bioactive molecules including biogenic amines, amino acids, peptides, lipids, nucleotides and proteins. As a result, GPCRs play a crucial role in many essential physiological processes like neurotransmission, cellular metabolism, secretion, cell growth, immune defense and differentiation. 

Plausible lipid-like peptides prebiotic molecular self-assembly in water Shuguang Zhang... 

Lipid-like peptides that form nanotubes and nanovesicles... 

Figure 20.4. Molecular models of cutaway structures formed from the lipid-like peptides with negatively charged heads and glycine tails. Each peptide is c. 2 nm in length. (A, C) Peptide vesicle with an area sliced away. (B, D) Peptide tubes. The glycines are packed inside the bilayer away from water, and the aspartic acids are exposed to water, much like other lipids and surfactants. The modeled dimension is 50-100 nm in diameter. Preliminary experiments suggest that the wall thickness may be c. 4-5 nm, implying that the wall may form a double layer, similar to phospholipids in cell membranes.

It is thus plausible that in the prebiotic world, under the influence of water, lipid-like peptides of various lengths might self-organize into distinct vesicles and tubes (regardless of sequence) that could enclose prebiotic rudimentary enzymes to isolate them from the environment. Thus, a diverse population of peptides and RNA might condense into complex structures that evolve to perform different functions. 

Figure 20.6. Images of lipid-like alanine and valine peptide enclosures. (A) Atomic-force microscopic (AFM) image of alanine tail and lysine head lipid-like peptide note the tube structures. (B) Transmission electron microscopic (TEM) image of valine tail and aspartic acid head lipid-like peptide note the tube structure with open and closed ends as well as vesicles.

Nagai, A., Nagai, Y., Qu, H. etal. (2007). Dynamic behaviors of lipid-like self-assembling peptide A(,l) and A(,K nanotubes. Journal of Nanoscience and Nanotechnology, 7, 2246-52. 

Yang, S. and Zhang, S. (2006) Self-assembling behavior of designer lipid-like peptides. Supramolecular Chemistry, 18, 389-96. 

It is unknown when and how cooperation with amino acids, peptides, and proteins started to evolve into an RNA-protein world. However, there is an upper size limit of RNAs, which is due to a threshold error of RNA replication. The heart of the core necessary to launch the process of chemical evolution towards the RNA world must have consisted of a number of pathways for the synthesis of organic molecules from CO2, N2, and H2. Additional pathways for the synthesis of amino acids, ribose, purines, pyrimidines, coenzymes, and lipids likely combined into this core. Overall, the number of pathways required to generate nucleotides is relatively small. Pyruvate, ammonia, carbon dioxide, ATP, and glyoxalate suffice to synthesize virtually the compounds required for metabolic cycles. It seems likely that once the RNA world existed that thereafter an RNA-Peptide world developed. Details are on the following website http //www.sciencedirect.com - Cell, Volumel36, Issue 4, page 599, and a description follow below. 

Figure 19.9. Bioconjugate ligand containing (1) peptide ligand (2) PEG tether, and (3) distearyldiaminobutyrate lipid like moiety.

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