Chemical modification strategy

As stated previously, peptidomimetic drug discovery was first advanced by molecular design concepts and chemical modification strategies focused on... 

Figure 2 Chemical modification strategies for iysine residues.

Figure 3 Chemical modification strategies for cysteine residues.

Figure 5 Chemical modification strategies for tyrosine residues.

Figure 6 Chemical modification strategies for tyrptophan residues.

As multiple copies of even the rarest amino acids are often present, cases exist in which none of the chemical modification strategies described above can be used to functionalize a single site. To address this challenge, many groups have developed reactions that take advantage of the unique chemical reactivities of the polypeptide termini. In addition to providing improvements in site selectivity, these methods have been used to form native-like peptide links in some instances. 

Figure 7 Chemical modification strategies of other amino acid residues.

Native semiconductor surfaces are fairly inactive from a catalysis perspective. Thus, noble metal or metal oxide islands have been implanted on photoelectrode surfaces as electron storage centers to drive multi-electron redox processes such as HER, photo-oxidation of H2O and photo-oxidation of HCl, HBr or HI. Examples of this sort of chemical modification strategy are also given in Table 3. 

Wang L, Gamez A, Sarkissian CN, Straub M, Patch MG, Won Han G, et al. Structure-based chemical modification strategy for enzyme replacement treatment of phenylketonuria. Mol Genet Metab 2005 86(l-2) 134-40. 

McNiven et al. [22] first demonstrated this guest directed chemical modification strategy. In their studies, an MAA/EGDMA polymer imprinted with testosterone (Fig. 3) was partially esterified with methyl iodide (Mel) and 1,8-diazabicyclo(5.4.0) undec-7-ene (DBU) both in the presence and absence of the... 

Scheme 8 Representation of the guest directed selective chemical modification strategy. The depth of the imprint in these models corresponds to the binding affinity of that site.

The similarity of the directly imprinted polymer and the selectively chemically modified MIP suggests that, in most cases, it will be easier to introduce selectivity by traditional molecular imprinting. However, there are situations in which the selective chemical modification strategy could be used to complement the normal imprinting process. For example, some molecules are not easily directly imprinted... 

One strategy that has become popular in recent years for controlling the chemistry of sp carbon electrodes involves electrochemically-assisted derivati-2ation. This field was recently reviewed by Downard [45], so only a brief synopsis is given herein. This relatively versatile chemical modification strategy involves either the oxidation or reduction of a precursor molecule to form a solution radical species at the electrode-electrolyte interface. This radical species then rapidly reacts at the surface to form a covalently attached admolecule. A wide range of molecules have been... 

The advantage of the latter reactions is that they are generally applicable to a variety of proteins, synthetic polymers and plasma-treated surfaces [82]. The overall surface density of the peptides can also be eontrolled easily via these chemical modification strategies, which can have a large impaet on eell proliferation and differentiation, particularly when coupled with manipulation of the chemical composition of the matrix material [85]. 

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