Molecules homologous

Kdn-gp appeared to be synthesized during relatively later stages of oogenesis, since it was undetectable in the oocyte 3 months prior to ovulation. Although the cell types that synthesize Kdn-gp have not been identified, it is most likely synthesized under hormonal control in some extraoocj e cells (i.e. follicle cells), secreted and partly incorporated into the second outermost layer of the vitelline envelope just before ovulation. Kdn-gp may thus be a molecule homologous to the oviduct glycoproteins of mammals that are reported to be secreted and partly incorporated into the egg surface [58-60]. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

In the methacrylate homologous series, the effect of side-chain bulkiness is just the opposite. In this case, however, the pendant groups are flexible and offer less of an obstacle to free rotation than the phenyl group in polystyrene. As chain bulk increases, molecules are wedged apart by these substituents, free volume increases, and Tg decreases. 

One of the most sensitive tests of the dependence of chemical reactivity on the size of the reacting molecules is the comparison of the rates of reaction for compounds which are members of a homologous series with different chain lengths. Studies by Flory and others on the rates of esterification and saponification of esters were the first investigations conducted to clarify the dependence of reactivity on molecular size. The rate constants for these reactions are observed to converge quite rapidly to a constant value which is independent of molecular size, after an initial dependence on molecular size for small molecules. The effect is reminiscent of the discussion on the uniqueness of end groups in connection with Example 1.1. In the esterification of carboxylic acids, for example, the rate constants are different for acetic, propionic, and butyric acids, but constant for carboxyUc acids with 4-18 carbon atoms. This observation on nonpolymeric compounds has been generalized to apply to polymerization reactions as well. The latter are subject to several complications which are not involved in the study of simple model compounds, but when these complications are properly considered, the independence of reactivity on molecular size has been repeatedly verified. 

The polarizabihties of molecules ia a homologous series iacrease steadily with increa sing aumbers of atoms. Therefore, the relative streagths of... 

Prolactin-Like Proteins. A number of prolactin-like proteins (PLPs), which ate distinct from the PLs, have been identified in mminants and rodents (11,23). Several cDNA transcripts coding for PLPs in catde have been identified (23). These transcripts code for proteins which possess about 40% sequence homology with bovine PRL 60% if conservative substitutions ate considered. Three glycosylated PLPs, ie, PLP-A, -B, and -C, ate produced during pregnancy in the rat (11). Two additional prolactin-related molecules have been identified in the mouse (24,25), ie, proliferin [92769-12-5] (PLF) and PLF-related protein [98724-27-7]. These ate not found in other rodents and may be unique to the mouse. The functional roles of PLPs remain to be deterrnined. 

Insulin and Amylin. Insulin is a member of a family of related peptides, the insulin-like growth factors (IGFs), including IGF-I and IGF-II (60) and amylin (75), a 37-amino acid peptide that mimics the secretory pattern of insulin. Amylin is deficient ia type 1 diabetes meUitus but is elevated ia hyperinsulinemic states such as insulin resistance, mild glucose iatolerance, and hypertension (33). Insulin is synthesized ia pancreatic P cells from proinsulin, giving rise to the two peptide chains, 4. and B, of the insulin molecule. IGF-I and IGF-II have stmctures that are homologous to that of proinsulin (see INSULIN AND OTHER ANTIDIABETIC DRUGS). 

Hoffmaim-La Roche has produced -carotene since the 1950s and has rehed on core knowledge of vitamin A chemistry for the synthesis of this target. In this approach, a five-carbon homologation of vitamin A aldehyde (19) is accompHshed by successive acetalizations and enol ether condensations to prepare the aldehyde (46). Metal acetyUde coupling with two molecules of aldehyde (46) completes constmction of the C q carbon framework. Selective reduction of the internal triple bond of (47) is followed by dehydration and thermal isomerization to yield -carotene (21) (Fig. 10). 

Ideal solution behavior is often approximated by solutions comprised of molecules not too different in size and of the same chemical nature. Thus, a mixture of isomers conforms very closely to ideal solution behavior. So do mixtures of adjacent members of a homologous series. 

Figure 2.19 Organization of polypeptide chains into domains. Small protein molecules like the epidermal growth factor, EGF, comprise only one domain. Others, like the serine proteinase chymotrypsin, are arranged in two domains that are required to form a functional unit (see Chapter 11). Many of the proteins that are involved in blood coagulation and fibrinolysis, such as urokinase, factor IX, and plasminogen, have long polypeptide chains that comprise different combinations of domains homologous to EGF and serine proteinases and, in addition, calcium-binding domains and Kringle domains.

One might expect these positions to exhibit a higher degree of amino acid conservation and hence sequence homology than the rest of the molecule. This is not, however, the case for distantly related molecules that have low sequence homology and derive from distantly related species. The sequence identity of these residues is no greater than in the rest of the... 

The two homologous repeats, each of 88 amino acids, at both ends of the TBP DNA-binding domain form two stmcturally very similar motifs. The two motifs each comprise an antiparallel p sheet of five strands and two helices (Figure 9.4). These two motifs are joined together by a short loop to make a 10-stranded p sheet which forms a saddle-shaped molecule. The loops that connect p strands 2 and 3 of each motif can be visualized as the stirmps of this molecular saddle. The underside of the saddle forms a concave surface built up by the central eight strands of the p sheet (see Figure 9.4a). Side chains from this side of the P sheet, as well as residues from the stirrups, form the DNA-binding site. No a helices are involved in the interaction area, in contrast to the situation in most other eucaryotic transcription factors (see below). 

Like Thr 124 and Thr 215, the Asn 69 and Asn 159 residues occupy equivalent positions in the two homologous motifs of TBP. By analogy with the symmetric binding of a dimeric repressor molecule to a palindromic sequence described in Chapter 8, the two motifs of TBP form symmetric sequence-specific hydrogen bonds to the quasi-palindromic DNA sequence at the center of the TATA box. The consensus TATA-box sequence has an A-T base pair at position 4, but either a T-A or an A-T base pair at the symmetry-related position 5, and the sequence is, therefore, not strictly palindromic. However, the hydrogen bonds in the minor groove can be formed equally well to an A-T base pair or to a T-A base pair, because 02 of thymine and N3 of adenine occupy nearly stereochemically equivalent positions, and it is sufficient, therefore, for the consensus sequence of the TATA box to be quasi-palindromic. 

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