Carrier group

So, the resistivities due to various scattering mechanisms add, as well as the contributions to the conductivity from different carrier groups. 

Further chain elongation of palmitic acid occurs by reactions similar to those just described, but CoA rather than ACP is the carrier group, ancl separate enzymes are needed for each step rather than a multienzyme synthase complex. 

Fig. 8.6. Two-step activation of pilocarpine prodrugs [123]. The prodrugs are diesters of pilocarpic acid (8.86). Enzymatic hydrolysis (Reaction a) cleaves the acyl carrier group. The product is a monoester of pilocarpic acid that undergoes cyclization to pilocarpine (8.87) upon intramolecular nucleophilic attack and loss of the alcohol carrier. 

Another feature of diacids of interest in prodrug design is that the free carboxy group of a drug R-COOH can be used to attach an additional carrier group R OH, e.g., R-CO-Cf -Cf -CO-OR. An example of this type has been reported for a lipid conjugate of testosterone, with R = 2-(l,3-dipalmi-toyljglyccryl [133] (see also Sect. 8.2.5). 

Diazoazoles find wide application in the preparation of azolo-triazenes, which have shown several biological activities expecially as antineoplastic agents. Triazenes are, in effect, latent diazo compounds because they decompose to give amino derivatives and diazonium salts so they can be employed as a carrier group for the diazo compounds (66JMC34). 

Comment on unresolved questions about the biosynthesis of cellulose, amylose, and amylopec-tin. What glycosyl carrier groups are required ... 

In 1907, Collie proposed that polymers of ketene (CH2=C=O) might be precursors of such compounds as orsellinic acid, a common constituent of lichens. The hypothesis was modernized in 1953 by Birch and Donovan, who proposed that several molecules of acetyl-CoA are condensed (Eq. 21-19) but without the two reduction steps required in biosynthesis of fatty acids (Fig. 17-12).329 As we now know they were correct in assuming that the condensation occurs via malonyl-CoA and an acyl carrier group of an enzyme. The resulting p-polyketone can react in various ways to give the large group of compounds known as polyketides. 

The properties that we evaluated predicted stability results only weakly. Perhaps under special conditions, such as specific carrier groups, such properties could give the desired correlations. However, for general carrier selection the correlations appear too weak, and therefore we should rely only on actual carrier stability tests. Reliance on correlations of these properties could lead to elimination of useful carriers or to selection of marginal ones. 

Table 20.2 Examples of common and less common carrier groups used in prodrug design.

Bioprecursors do not imply a temporary linkage between the active principle and a carrier group, but result from a molecular modification of the active principle itself. This modification generates a new compound, which is a substrate for metabolizing enzymes, leading to a metabolite that is the expected active principle. This approach exemplifies the active metabolite concept in a provisional way (e.g. sulindac, fenbufen, acyclovir, losartan). 

The biomembrane passage of a drug depends primarily on its physicochemical properties and especially on its partition coefficient (Chapters 22 and 34). Thus, the transient attachment of a lipophilic carrier group to an active principle can provide a better bioavailability, mostly by facifitating cell membrane crossing by passive diffusion. Peroral absorption, as well as rectal absorption, ocular drug delivery and dermal drug delivery, are dependent on passive diffusion. Finally, lipophilic carriers can sometimes be useful to reduce first-pass metabolism. ... 

Constitution Active principle + carrier group No carrier group... 

Table 13.14 Examples of Common and Less C nmon Carrier Groups Used in Prodrt Design...

Carrier groups linked to a carboxylic group (R-COOH)... 

Amides of amino acids (e.g., glycine), e.g., R-CO-NH-CH(R )-COOH Carrier groups linked to an amino or amido group (RR -NH)... 

Numerous carrier-linked prodrugs have been prepared from drugs containing an adequate functional group. Without aiming at comprehensiveness, a list of common and less common carrier groups is given in Table 13.14 for... 

Aziridine derivatives where the aziridine groups are linked to nitrogen-containing heterocyclic carrier groups are 2,6-bis(l-aziridinyl)pyrazine (ENT-50457, 17), 4,8-bis(l-aziridinyl)pyrimidino-[5,4d]-pyrimidine (ENT-50792,18) and 2,4,6-tris(l-aziridinyl)-j-triazine (triethylene-melamine, tretamine, 19). 

Transcellular Process by which matter passes through the cell membranes to reach the other side of a tissue. Transport electron carriers Group of carriers that catalyze electron flow across a membrane. 

The carrier prodrugs result from a temporary linkage of the active molecule with a transport moiety that is frequently of hpophilic nature. A simple hydrolytic reaction cleaves this transport moiety at the correct moment (e.g. pivampicillin, bacampicillin). Such prodrags are per se less active than the parent compounds or even inactive. The transport moiety (carrier group) will be chosen for its nontoxicity and its ability to ensure the release of the active principle with efficient kinetics. 

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