Life during a golden age of peptide chemistry. The concept and development of solid-phase peptide synthesis, B. Merrifield, ACS, Washington DC, 1993, 314 pp., $24.95, ISBN 0-8412-1842-0

Protecting groups like Fmoc and coupling both steps are essential to monitoring the Fmoc SPPS (Solid Phase Peptide Synthesis) reaction completion. Reliable methods are used to detect the unreacted number of amino groups for monitoring these two essential reaction steps of coupling and cleavage. The ability to detect the complete coupling, incomplete coupling or failure of coupling we use many colour tests in the laboratory and based on this the Fmoc peptide chemistry allows the control of the completion of the Fmoc cleavage. The most important test used is the Kaiser test and highly recommended to monitor the coupling and cleavage steps. If the result of colour tests is positive after coupling, then the second coupling should be performed. Then again use the colour test to detect the level of coupling. If the result is still slightly positive, repeat coupling with the smaller modification of reagents such as used PyBOP instead of HOBT AND HOAT. These colour tests help in revealing the presence of unreacted amino-functional groups. Thus, we need to block these free N-terminal of amino- acids which help in avoiding the making of deletion of sequence.

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Green Solid-Phase Peptide Synthesis (GSPPS) 3. Green Solvents for Fmoc Removal in Peptide Chemistry

Organic Process Research & Development ◽

10.1021/acs.oprd.6b00439 ◽

2017 ◽

Vol 21 (3) ◽

pp. 365-369 ◽

Cited By ~ 26

Author(s):

Yahya E. Jad ◽

Thavendran Govender ◽

Hendrik G. Kruger ◽

Ayman El-Faham ◽

Beatriz G. de la Torre ◽

...

Keyword(s):

Peptide Synthesis ◽

Solid Phase ◽

Solid Phase Peptide Synthesis ◽

Green Solvents ◽

Peptide Chemistry

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Cyanosulfurylides (CSY): Carboxylic Acid Protecting Groups That Prevent Aspartimide Formation During Peptide Synthesis

10.26434/chemrxiv.9767027.v1 ◽

2019 ◽

Author(s):

Kevin Neumann ◽

Jakob Farnung ◽

Simon Baldauf ◽

Jeffrey Bode

Keyword(s):

Peptide Synthesis ◽

Solid Phase ◽

Bond Cleavage ◽

Solid Phase Peptide Synthesis ◽

Academic Research ◽

Industrial Applications ◽

Protecting Group ◽

Peptide Chemistry ◽

Formidable Challenge ◽

Aspartimide Formation

Peptide chemistry has made great progress in the last decades but the frequent occurrence of aspartimide formation during peptide synthesis remains a formidable challenge. Aspartimide formation leads to low yields in addition to costly purification steps or even inaccessible peptide sequences, hindering both academic research and industrial applications. Here, we report a new alternative approach to address this longstanding challenge of solid phase peptide synthesis by utilizing cyanosulfurylides to mask carboxylic acids by a stable C–C bond. These functional groups – formally zwitterionic species – are exceptionally stable to all common manipulations and impart improved solubility and processing during peptide synthesis. Deprotection is readily and rapidly achieved under mild, aqueous conditions with electrophilic halogenating agents via a highly selective C–C bond cleavage reaction. This new protecting group was employed for the synthesis a range of peptides and proteins including teduglutide, ubiquitin, and LDLa – a peptide that was not accessible on solid-phase peptide synthesis before due to three aspartimide-prone motifs. This protecting group strategy has the potential to overcome one of the most difficult aspects of modern peptide chemistry.

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Cyanosulfurylides (CSY): Carboxylic Acid Protecting Groups That Prevent Aspartimide Formation During Peptide Synthesis

10.26434/chemrxiv.9767027 ◽

2019 ◽

Author(s):

Kevin Neumann ◽

Jakob Farnung ◽

Simon Baldauf ◽

Jeffrey Bode

Keyword(s):

Peptide Synthesis ◽

Solid Phase ◽

Bond Cleavage ◽

Solid Phase Peptide Synthesis ◽

Academic Research ◽

Industrial Applications ◽

Protecting Group ◽

Peptide Chemistry ◽

Formidable Challenge ◽

Aspartimide Formation

Peptide chemistry has made great progress in the last decades but the frequent occurrence of aspartimide formation during peptide synthesis remains a formidable challenge. Aspartimide formation leads to low yields in addition to costly purification steps or even inaccessible peptide sequences, hindering both academic research and industrial applications. Here, we report a new alternative approach to address this longstanding challenge of solid phase peptide synthesis by utilizing cyanosulfurylides to mask carboxylic acids by a stable C–C bond. These functional groups – formally zwitterionic species – are exceptionally stable to all common manipulations and impart improved solubility and processing during peptide synthesis. Deprotection is readily and rapidly achieved under mild, aqueous conditions with electrophilic halogenating agents via a highly selective C–C bond cleavage reaction. This new protecting group was employed for the synthesis a range of peptides and proteins including teduglutide, ubiquitin, and LDLa – a peptide that was not accessible on solid-phase peptide synthesis before due to three aspartimide-prone motifs. This protecting group strategy has the potential to overcome one of the most difficult aspects of modern peptide chemistry.

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A Strategy for Thioamide Incorporation During Fmoc Solid-Phase Peptide Synthesis with Robust Stereochemical Integrity

10.26434/chemrxiv.8206247.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

luis camacho III ◽

Bryan J. Lampkin ◽

Brett VanVeller

Keyword(s):

Amino Acid ◽

Functional Groups ◽

Peptide Synthesis ◽

Solid Phase ◽

Solid Phase Peptide Synthesis ◽

Side Chains ◽

Amino Acid Side Chains ◽

Peptide Elongation

We describe a method to protect the sensitive stereochemistry of the thioamide—in analogy to the protection of the functional groups of amino acid side chains—in order to preserve the thioamide moiety during peptide elongation.<br>

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