- Towards a circular bis-peptide nucleic acid
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En route to a circular bis-PNA molecule, we have synthesized and characterized the DNA binding of several "clamp"-type bis-PNAs. In order to incorporate charge into a circular PNA, a new linker based on the achiral 2-aminoethylglycine has been used.
- Hudson,Tse
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Read Online
- Peptide Nucleic Acid with Double Face: Homothymine-Homocytosine Bimodal Cα-PNA (bm-Cα-PNA) Forms a Double Duplex of the bm-PNA2:DNA Triplex
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Cα-bimodal peptide nucleic acids (bm-Cα-PNA) are PNAs with two faces and are designed homologues of PNAs in which each aminoethylglycine (aeg) repeating unit in the standard PNA backbone hosts a second nucleobase at Cα through a spacer chain with a triazole linker. Such bm-Cα-PNA with mixed sequences can form double duplexes by simultaneous binding to two complementary DNAs, one to the base sequence on t-amide side and the other to the bases on the Cα side chain. The synthesis of bm-Cα-PNA with homothymine (T7) on the t-amide face and homocytosine (C5) on the Cα side chain through the triazole linker was achieved by solid phase synthesis with the global click reaction. In the presence of complementary DNAs dA8 and dG6 at neutral pH, bm-Cα-PNA 1 forms a higher order pentameric double duplex of a triplex composed of two bm-Cα-PNA-C5:dG5 duplexes built on a core (bm-Cα-PNA-T7)2:dA8 triplex. Circular dichroism studies showed that assembly can be achieved by either triplex first and duplex later or vice versa. Isothermal titration calorimetry data indicated that the assembly is driven by favorable enthalpy. These results validate concurrent multiple complex formation by bimodal PNAs with additional nucleobases at Cα or Cγon the aeg-PNA backbone and open up ways to design programmed supramolecular assemblies.
- Gupta, Manoj Kumar,Madhanagopal, Bharath Raj,Ganesh, Krishna N.
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supporting information
p. 414 - 428
(2020/12/22)
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- CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
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The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases.
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Paragraph 0454
(2015/02/25)
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- CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
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The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1 ) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases.
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Page/Page column 129
(2013/10/08)
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- Convenient synthesis and cyclization of dimeric abasic PNA
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The synthesis of an abasic PNA-based dimer block has been achieved. An alkyl chain stapling the two base sites conformationally restricts the PNA backbone, and serves as an example of preorganization by direct base site linkage. Other possible examples of
- Cooper, Daniel C.,Suggs, J. William
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supporting information
p. 6943 - 6945
(2013/01/15)
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- Synthetic procedures for peptide nucleic acids
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A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.
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- Peptide nucleic acids having antibacterial activity
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Methods of and compositions for killing or inhibiting the growth of a bacteria are disclosed. The methods comprise the use of peptide nucleic acids that are targeted to mRNA and/or rRNA. In certain embodiments, methods include the use of one or more separate antibiotics.
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- Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
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A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases, including 2,6-diaminopurine, attached to a polyamide backbone, and contain alkyl amine side chains.
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- Linked peptide nucleic acids
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Novel peptide nucleic acids and novel linked peptide nucleic acids, form triple stranded structures with nucleic acids. The peptide nucleic acids include ligands such as naturally occurring nucleobases attached to the peptide backbone through a suitable linker. Other nucleobases including C-pyrimidines and iso-pyrimidines can be used as the ligands in Hoogsteen strands to increase binding affinity. Two peptide nucleic acid strands are joined together with a linker to form a bis-peptide nucleic acid. The individual strands of the peptide nucleic acids in the bis compounds can be oriented either parallel or antiparallel to each other.
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- Peptide nucleic acids
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Novel peptide nucleic acids and novel linked peptide nucleic acids, form triple stranded structures with nucleic acids. The peptide nucleic acids include ligands such as naturally occurring nucleobases attached to a peptide backbone through a suitable linker. Other nucleobases including C-pyrimidines and iso-pyrimidines can be used as the ligands in Hoogsteen strands to increase binding affinity. Two peptide nucleic acid strands are joined together with a linker to form a bis-peptide nucleic acid. The individual strands of the peptide nucleic acids in the bis compounds can be orientated either parallel or antiparallel to each other.
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- Peptide nucleic acids having 2,6-diaminopurine nucleobases
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A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone. Some PNAs of the invention also contain C1-C8alkylamine side chains.
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- Bioactive pseudopeptidic analogues and cyclostereoisomers of osteogenic growth peptide C-terminal pentapeptide, OGP(10-14)
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The osteogenic growth peptide (OGP) is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury. When administered in vivo, OGP stimulates osteogenesis and hematopoiesis. The C-terminal pentapeptide OGP(10-14) is the minimal amino acid sequence that retains the full OGP-like activity. Apparently, it is also the physiologic active form of OGP. Residues Tyr10, Phe12, Gly13, and Gly14 of OGP are essential for the OGP(10-14) activity. The present study explored the functional role of the peptide bonds, carboxyl and amino terminal groups, and conformational freedom in OGP(10-14). Transformations replacing the peptide bonds with surrogates such as ψ(CH2NH), ψ(CONMe), and ψ(CH2CH2) demonstrated that amide bonds do not contribute significantly to OGP(10-14) bioactivity. End-to-end cyclization yielded the fully bioactive cyclic pentapeptide c(Tyr-Gly-Phe-Gly-Gly). The retroinverso analogue c(Gly-Gly-phe-Gly-tyr), a cyclostereoisomer of c(Tyr-Gly-Phe-Gly-Gly), is at least as potent as the parent cyclic pentapeptide. The unique structure-activity relations revealed in this study suggest that the spatial presentation of the Tyr and Phe side chains has a major role in the productive interaction of OGP(10-14) and its truncated and conformationally constrained analogues with their cognate cellular target.
- Chen, Yu-Chen,Muhlrad, Andras,Shteyer, Arie,Vidson, Marina,Bab, Itai,Chorev, Michael
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p. 1624 - 1632
(2007/10/03)
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- Antibacterial and antibiotic methods using peptide nucleic acids and pharmaceutical compositions therefor
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Methods of and compositions for killing or inhibiting the growth of a bacteria are disclosed. The methods comprise the use of peptide nucleic acid that is targeted to mRNA and/or rRNA. In certain embodiments, methods include the use of one or more separate antibiotics.
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- Double-stranded peptide nucleic acids
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A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.
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- Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
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A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain C1 -C8 alkylamine side chains. Methods of enhancing the solubility, binding affinity and sequence specificity of PNAs are provided.
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- Peptide nucleic acids having amino acid side chains
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A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain alkylamine side chains.
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- Peptide nucleic acids
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A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.
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- Enkephalin analogues
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Compounds corresponding in structure to enkephalin or polypeptide analogues thereof, wherein one or more peptide links of the enkephalin or analogue is represented by a group or groups the same or different selected from dimethylene, hydroxydimethylene, methylene-imino and ketomethylene groups and/or wherein adjacent peptide bond nitrogen atoms are linked by a carbonyl or thiocarbonyl group.
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- Enkephalin analogues
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Compounds corresponding in structure to enkephalin or polypeptide analogues thereof, wherein one or more peptide links of the enkephalin or analogue is represented by a group or groups the same or different selected from dimethylene, methylene-imino and keto-methylene groups.
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- Aminoethylglycine containing polypeptides
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Novel somatostatin analogues containing one or more aminoethylglycyl residues at the amino and/or carboxyl terminus or in the ring position are described. The compounds are potent and long lasting inhibitors of gastric acid secretion.
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