Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
Peptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA’s chemistry, optimization of structure and function, applications as probes and diagnostics, and...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Beilstein-Institut
2021-07-01
|
| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.17.116 |
| _version_ | 1830178040246697984 |
|---|---|
| author | Nikita Brodyagin Martins Katkevics Venubabu Kotikam Christopher A. Ryan Eriks Rozners |
| author_facet | Nikita Brodyagin Martins Katkevics Venubabu Kotikam Christopher A. Ryan Eriks Rozners |
| author_sort | Nikita Brodyagin |
| collection | DOAJ |
| description | Peptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA’s chemistry, optimization of structure and function, applications as probes and diagnostics, and attempts to develop new PNA therapeutics. The discussion starts with a brief review of PNA’s binding modes and structural features, followed by the most impactful chemical modifications, PNA enabled assays and diagnostics, and discussion of the current state of development of PNA therapeutics. While many modifications have improved on PNA’s binding affinity and specificity, solubility and other biophysical properties, the original PNA is still most frequently used in diagnostic and other in vitro applications. Development of therapeutics and other in vivo applications of PNA has notably lagged behind and is still limited by insufficient bioavailability and difficulties with tissue specific delivery. Relatively high doses are required to overcome poor cellular uptake and endosomal entrapment, which increases the risk of toxicity. These limitations remain unsolved problems waiting for innovative chemistry and biology to unlock the full potential of PNA in biomedical applications. |
| first_indexed | 2024-12-17T19:34:31Z |
| format | Article |
| id | doaj.art-0136f8ae13954868a0c39cb0a71d2dcc |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-17T19:34:31Z |
| publishDate | 2021-07-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-0136f8ae13954868a0c39cb0a71d2dcc2022-12-21T21:35:10ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972021-07-011711641168810.3762/bjoc.17.1161860-5397-17-116Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applicationsNikita Brodyagin0Martins Katkevics1Venubabu Kotikam2Christopher A. Ryan3Eriks Rozners4Department of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, United StatesLatvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, LatviaDepartment of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, United StatesDepartment of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, United StatesDepartment of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, United StatesPeptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA’s chemistry, optimization of structure and function, applications as probes and diagnostics, and attempts to develop new PNA therapeutics. The discussion starts with a brief review of PNA’s binding modes and structural features, followed by the most impactful chemical modifications, PNA enabled assays and diagnostics, and discussion of the current state of development of PNA therapeutics. While many modifications have improved on PNA’s binding affinity and specificity, solubility and other biophysical properties, the original PNA is still most frequently used in diagnostic and other in vitro applications. Development of therapeutics and other in vivo applications of PNA has notably lagged behind and is still limited by insufficient bioavailability and difficulties with tissue specific delivery. Relatively high doses are required to overcome poor cellular uptake and endosomal entrapment, which increases the risk of toxicity. These limitations remain unsolved problems waiting for innovative chemistry and biology to unlock the full potential of PNA in biomedical applications.https://doi.org/10.3762/bjoc.17.116antisensechemical modificationsdiagnosticspeptide nucleic acidpna |
| spellingShingle | Nikita Brodyagin Martins Katkevics Venubabu Kotikam Christopher A. Ryan Eriks Rozners Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications Beilstein Journal of Organic Chemistry antisense chemical modifications diagnostics peptide nucleic acid pna |
| title | Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications |
| title_full | Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications |
| title_fullStr | Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications |
| title_full_unstemmed | Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications |
| title_short | Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications |
| title_sort | chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications |
| topic | antisense chemical modifications diagnostics peptide nucleic acid pna |
| url | https://doi.org/10.3762/bjoc.17.116 |
| work_keys_str_mv | AT nikitabrodyagin chemicalapproachestodiscoverthefullpotentialofpeptidenucleicacidsinbiomedicalapplications AT martinskatkevics chemicalapproachestodiscoverthefullpotentialofpeptidenucleicacidsinbiomedicalapplications AT venubabukotikam chemicalapproachestodiscoverthefullpotentialofpeptidenucleicacidsinbiomedicalapplications AT christopheraryan chemicalapproachestodiscoverthefullpotentialofpeptidenucleicacidsinbiomedicalapplications AT eriksrozners chemicalapproachestodiscoverthefullpotentialofpeptidenucleicacidsinbiomedicalapplications |