Antiparallel template

DNA synthesis is catalysed by DNA polymerases and requires the precursor dNTPs (dATP, dGTP, dCTP and dTTP, each of these existing as Mg2+ complexes), a template (i.e. the dsDNA being copied) and a primer (an initial deoxyribose 3 -OH to enable the reaction to insert the first new nucleotide). The reaction proceeds in a 5 to 3 direction, that is, at the end of the synthesis there is a vacant deoxyribose 3 -OH. The fidelity of the replication process is based on the incoming nucleotides base pairing with the correct base on the antiparallel template. DNA synthesis is semi-conservative (i.e. the newly synthesized strand partners its antiparallel complementary strand) and is bidirectional (because both original strands are replicated). 

All DNA polymerases are single-minded—they can do it only one way. Each dNTP (deoxynucleoside triphosphate) is added to the 3 -OH group of the growing chain so that all chains grow from the 5 end in the dirction 5 to 3. Since strands are antiparallel, the template strand is read in the 3 to 5 direction. This is true of both DNA and RNA synthesis. Most of what you need to know about DNA replication can be summarized in a single picture. 

RNA polymerase moves along the template strand in the 3 to 5 direction as it synthesizes the RNA product in the 5 to 3 direction using NTPs (ATP, GTP, CTP, UTP) as substrates. RNA polymerase does not proofread its work. The RNA product is complementary and antiparallel to the template strand. 

The answer is E. RNA is antiparallel and complementary to the template strand. Also remember that, by convention, aU base sequences are written in the 5 to 3 direction regardless of the direction in which the sequence may actually be used in the cell. 

Relationship of RNA transcript to DNA RNA is antiparallel and complementary to DNA template strand RNA is identical (except U substitutes for T) to DNA coding strand ... 

RNA polymerase requires DNA for activity and is most active when bound to a double-stranded DNA. As noted above, only one of the two DNA strands serves as a template. The template DNA strand is copied in the 3 —>5 direction (antiparallel to the new RNA strand), just as in DNA replication. Each nucleotide in the newly formed RNA is selected by Watson-Criclc base-pairing interac-... 

When the two strands of the DNA double helix are separated, each can serve as a template for the replication of a new complementary strand. This produces two daughter molecules, each of which contains two DISA strands with an antiparallel orientation (see Figure 29.3). This process is called semiconservative replication because, although the parental duplex is separated into two halves (and, therefore, is not "conserved" as an entity), each of the individual parental strands remains intact in one of the two new duplexes (Figure 29.8). The enzymes involved in the DlsA replication process are template-directed polymerases that can synthesize the complementary sequence of each strand with extraordinary fidelity. The reactions described in this section were first known fiom... 

The DNA polymerases responsible for copying the DNA templates are only able to "read" the parental nucleotide sequences in the 3 —>5 direction, and they synthesize the new DNA strands in the 5 —>3 (antiparallel) direction. Therefore, beginning with one parental double helix, the two newly synthesized stretches of nucleotide chains must grow in opposite directions—one in the 5 - 3 direction toward the replication fork and one in the 5 —>3 direction away from the replication fork (Figure 29.14). This feat is accomplished by a slightly different mechanism on each strand. 

In the present example we have examined the sequence in mRNA. In the DNA there are two strands. One is the coding strand (also called the nontranscribing or nontranscribed strand), which has a sequence that corresponds to that in the mRNA and the one that is given in Fig. 5-4. The second antiparallel and complementary strand can be called the template strand or the noncoding, transcribing, or transcribed strand.372 The mRNA that is formed is sometimes referred to as a sense strand. The complementary mRNA, which corresponds in sequence to the noncoding strand of DNA, is usually called antisense RNA. 

In addition to incorporating the 4-(2-aminoethyl)dibenzofuran-6-propanoic acid template into small peptides where a reverse turn is desired, we have also recently incorporated this template into a mini-protein called the PIN WW domain. WW domains have a three-stranded antiparallel p-sheet structure that mediates intracellular protein-protein interactions. 31 Substitution of this 3-turn mimetic into loop 1 of the PIN WW domain leads to a folded, three-stranded, antiparallel p-sheet structure with a stability indistinguishable from that of the all a-amino acid sequence. The template-incorporated PIN WW domain (11) was synthesized by an Fmoc-based solid-phase peptide synthesis strategy (Scheme 8), utilizing N-Fmoc-protected 4-(2-aminoethyl)dibenzofuran-6-propanoic acid 10. 11 The synthesis of 10, similar to that of 8, has been published.1 1 ... 

In biological recognition phenomena, protein-protein interactions are of primary importance. In an attempt to mimic these processes, LaBrenz and Kelly [51] synthesized the peptidic host 64. In this receptor, the dibenzofuran template separates the two peptide units by roughly 10 A and allows for the complexation of a guest peptide (65), as depicted in Fig. 21. The complex first forms a three-stranded, antiparallel /J-sheet that is stabilized by hydrogen bonds, electrostatic interactions, and aromatic-aromatic interactions between the dibenzofuran and the benzamide moieties. This complex can further self associate to form more complex structures. This example shows that structurally defined peptide nanostructures can interfere with biological recognition processes and potentially have therapeutic applications. 

Antiparallel Four-Helix-Bundle Template-Assembled Synthetic Protein Molecules... 

The cyclic decapeptide template contains four cysteine residues with different protecting groups which allows for the coupling of the unprotected helices in aqueous solution carrying bromoacetyl units, either at the N-terminus or the e-amino group of a C-terminal lysine residue/1091101 resulting in an antiparallel arrangement (Scheme 18). 

The use of oxime bond formation with orthogonal protection techniques allows the efficient construction of an antiparallel four-helix-bundle TASP122 (Scheme 19) by condensing amphiphilic peptide blocks, containing aldehyde functions at the C- or N-terminus, to a topological template functionalized with selectively addressable aminooxy acetic acid moieties, t20,22,971... 

The template used for generating P-sheet structures described in this section is based on the structure of gramicidin S (1, Scheme 1). Gramicidin S is a head-to-tail cyclic decapeptide discovered over 50 years ago and has the sequence c[-Val-Om-Leu-D-Phe-Pro-]2. 13 The tertiary structure of gramicidin S has since been elucidated and found to exist in a P-sheet/p-turn conformation. 14,15 As shown in Scheme 1, two antiparallel P-strands containing the Val-Om-Leu sequence are held in place by two type II P-tums defined by the D-Phe-Pro sequence. Val and Leu residues occupy H-bonded sites while Orn residues are located in non-H-bonded sites. 

Although successful attempts to develop templates for fj-sheet structures are rare (see also Chapter 2.4), Kemp and coworkers introduced an epindolidione-based template that mimics the central strand of a fj-sheet by appropriately orienting three hydrogen bonds to enforce an extended conformation on the attached peptide chains, as shown in Figure 1.2.2 with the model system III [6], Direct attachment of peptide chains to the template leads to the formation of a parallel fj-sheet mimic, whereas antiparallel fj-sheet models can be obtained by incorporation of two urea groups for attachment of the peptide chains [7]. 

Because only one strand can serve as a template for synthesis in the 5 to 3 direction (the template goes in the 3 to 5 direction, because the double helix is antiparallel), only one strand, the leading strand, can be elongated continuously. Ahead of the replication fork, DNA gyrase (topoisomerase II) helps unwind the DNA double helix and keep the double strands from tangling during replication. 

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