scholarly journals Omniligase-1: A Powerful Tool for Peptide Head-to-Tail Cyclization

2017 ◽  
Vol 359 (12) ◽  
pp. 2050-2055 ◽  
Author(s):  
Marcel Schmidt ◽  
Ana Toplak ◽  
Peter J. L. M. Quaedflieg ◽  
Hans Ippel ◽  
Gaston J. J. Richelle ◽  
...  
Keyword(s):  
Head To Tail Cyclization

scholarly journals Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation

2015 ◽  
Vol 6 (8) ◽  
pp. 4889-4896 ◽  
Author(s):  
Florian Rohrbacher ◽  
Gildas Deniau ◽  
Anatol Luther ◽  
Jeffrey W. Bode
Keyword(s):  
Cyclic Peptides ◽  
Mechanistic Study ◽  
Coupling Reagents ◽  
Head To Tail Cyclization

The α-ketoacid–hydroxylamine (KAHA) ligation enables the direct cyclization of unprotected peptides upon cleavage, without coupling reagents or purification of precursors. We report the synthesis of a library of 24 cyclic peptides and a detailed mechanistic study.

Synthesis of Dichotomin A: Use of a Penicillamine-Derived Pseudoproline to Furnish Native Valine Residues

2015 ◽  
Vol 68 (4) ◽  
pp. 627 ◽  
Author(s):  
Michelle S. Y. Wong ◽  
Deni Taleski ◽  
Katrina A. Jolliffe
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Side Chain ◽  
Linear Peptide ◽  
Cyclic Hexapeptide ◽  
Peptide Precursors ◽  
Head To Tail Cyclization

The total synthesis of cyclic hexapeptide dichotomin A from linear peptide precursors containing penicillamine-derived pseudoproline residues is reported. The incorporation of a pseudoproline residue led to a faster reaction and higher head-to-tail cyclization yields in comparison to linear precursors containing the native valine residue. However, deprotection of the pseudoproline resulted in significant amounts of a by-product in which a threonine side chain had undergone dehydration, resulting in a low overall yield of the natural product.

Synthesis of Nanotubule-Forming Cyclic Octapeptides via an Fmoc Strategy

1998 ◽  
Vol 51 (7) ◽  
pp. 535 ◽  
Author(s):  
Martina E. Polaskova ◽  
John N. Lambert ◽  
Nicholas J. Ede
Keyword(s):  
Aqueous Solutions ◽  
Infrared Absorption ◽  
Structural Studies ◽  
Protection Strategy ◽  
Fmoc Chemistry ◽  
Orthogonal Protection ◽  
Fmoc Strategy ◽  
Cyclic Octapeptide ◽  
Head To Tail Cyclization ◽  
Hydrogen Bonded

New syndiotactic cyclic octapeptides, namely cyclo(–D-Phe-L-Asp–D-Phe–L-Asn–D-Phe–L-Asp–D-Phe–L-Asn–) (1) and cyclo(–D-N-MeAla–L-Asp–D-N-MeAla–L-Asn–D-N-MeAla–L-Asp–D-N-MeAla–L-Asn–) (2), have been prepared, and preliminary structural studies have been conducted. The synthesis of the linear peptides was performed by using Fmoc chemistry, and head-to-tail cyclization was accomplished by using an orthogonal protection strategy and a support-bound cyclization step. Acidification of aqueous solutions of cyclic octapeptide (1) initiated formation of needlelike crystals whose morphology and infrared absorption behaviour suggested that they were hydrogen-bonded nanotubular aggregates of (1).

2-Propanephosphonic acid anhydride (T3P)-mediated segment coupling and head-to-tail cyclization of sterically hindered peptides

1999 ◽  
pp. 1847-1848 ◽  
Author(s):  
Jana Klose ◽  
Michael Bienert ◽  
Christoph Mollenkopf ◽  
Detlef Wehle ◽  
Chong-wu Zhang ◽  
...  
Keyword(s):  
Acid Anhydride ◽  
Sterically Hindered ◽  
Head To Tail Cyclization

Soluble Tag-Assisted Peptide Head-to-Tail Cyclization: Total Synthesis of Mahafacyclin B

2013 ◽  
Vol 15 (6) ◽  
pp. 1155-1157 ◽  
Author(s):  
Yuko Fujita ◽  
Shuji Fujita ◽  
Yohei Okada ◽  
Kazuhiro Chiba
Keyword(s):  
Total Synthesis ◽  
Head To Tail Cyclization

scholarly journals Stability Enhancement of a Dimeric HER2-Specific Affibody Molecule through Sortase A-Catalyzed Head-to-Tail Cyclization

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2874
Author(s):  
Kristina Westerlund ◽  
Anders Myrhammar ◽  
Hanna Tano ◽  
Maxime Gestin ◽  
Amelie Eriksson Karlström
Keyword(s):  
Specific Binding ◽  
Cyclic Dimer ◽  
Sortase A ◽  
Apparent Difference ◽  
Her2 Receptor ◽  
Linear Dimer ◽  
Fold Reduction ◽  
Before And After ◽  
The Stability ◽  
Head To Tail Cyclization

Natural backbone-cyclized proteins have an increased thermostability and resistance towards proteases, characteristics that have sparked interest in head-to-tail cyclization as a method to stability-enhance proteins used in diagnostics and therapeutic applications, for example. In this proof-of principle study, we have produced and investigated a head-to-tail cyclized and HER2-specific ZHER2:342 Affibody dimer. The sortase A-mediated cyclization reaction is highly efficient (>95%) under optimized conditions, and renders a cyclic ZHER3:342-dimer with an apparent melting temperature, Tm, of 68 °C, which is 3 °C higher than that of its linear counterpart. Circular dichroism spectra of the linear and cyclic dimers looked very similar in the far-UV range, both before and after thermal unfolding to 90 °C, which suggests that cyclization does not negatively impact the helicity or folding of the cyclic protein. The cyclic dimer had an apparent sub-nanomolar affinity (Kd ~750 pM) to the HER2-receptor, which is a ~150-fold reduction in affinity relative to the linear dimer (Kd ~5 pM), but the anti-HER2 Affibody dimer remained a high-affinity binder even after cyclization. No apparent difference in proteolytic stability was detected in an endopeptidase degradation assay for the cyclic and linear dimers. In contrast, in an exopeptidase degradation assay, the linear dimer was shown to be completely degraded after 5 min, while the cyclic dimer showed no detectable degradation even after 60 min. We further demonstrate that a site-specifically DyLight 594-labeled cyclic dimer shows specific binding to HER2-overexpressing cells. Taken together, the results presented here demonstrate that head-to-tail cyclization can be an effective strategy to increase the stability of an Affibody dimer.

scholarly journals A novel computational method for head-to-tail peptide cyclization: application to urotensin II

2022 ◽  
Author(s):  
Yasaman Karami ◽  
Samuel Murail ◽  
Julien Giribaldi ◽  
Benjamin Lefranc ◽  
Jerome Leprince ◽  
...  
Keyword(s):  
Amino Acid ◽  
Large Scale ◽  
Protein Structures ◽  
Computational Method ◽  
Urotensin Ii ◽  
Peptide Cyclization ◽  
Linear Peptide ◽  
Structure Relationship ◽  
Head To Tail Cyclization

Peptides have recently re-gained interest as therapeutic candidates but their development remains confronted with several limitations including low bioavailability. Backbone head-to-tail cyclization is one effective strategy of peptide-based drug design to stabilize the conformation of bioactive peptides while preserving peptide properties in terms of low toxicity, binding affinity, target selectivity and preventing enzymatic degradation. However, very little is known about the sequence-structure relationship requirements of designing linkers for peptide cyclization in a rational manner. Recently, we have shown that large scale data-mining of available protein structures can lead to the precise identification of protein loop conformations, even from remote structural classes. Here, we transpose this approach to head-to-tail peptide cyclization. Firstly we show that given a linker sequence and the conformation of the linear peptide, it is possible to accurately predict the cyclized peptide conformation improving by over 1 A over pre-existing protocols. Secondly, and more importantly, we show that is is possible to elaborate on the information inferred from protein structures to propose effective candidate linker sequences constrained by length and amino acid composition, providing the first framework for the rational peptide head-to-tail cyclization. As functional validation, we apply it to the design of a head-to-tail cyclized derivative of urotensin II, an 11-residue long peptide which exerts a broad array of biologic activities, making its cognate receptor a valuable and innovative therapeutic or diagnostic target. We propose a three amino acid candidate linker, leading to the first synthesized 14-residue long cyclic UII analogue with excellent retention of in vitro activity.

“Head-to-Tail” Cyclization of Hexapeptides Using Different Coupling Reagents

1993 ◽  
Vol 1993 (5) ◽  
pp. 497-501 ◽  
Author(s):  
Susanne Zimmer ◽  
Eike Hoffmann ◽  
Günther Jung ◽  
Horst Kessler
Keyword(s):  
Coupling Reagents ◽  
Head To Tail Cyclization
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