Synthesis of a Novel PTH1–34 Analog with Increased Human Serum Albumin Affinity

Parathyroid hormone (PTH)1–34 is an effective peptide drug for osteoporosis therapy. However, the half-life of PTH1–34 in vivo is short, leading to the need for frequent injections of this drug during its treatment. To prolong the half-life of PTH1–34, a novel PTH1–34 analog was generated based on fatty acid generation, and its synthesis process included recombinant protein expression, side-chain modification, and peptide decoration. The PTH1–34 variant was expressed in Escherichia coli, with a single Lys (position 27) retained as a modification site. The side chain, –AEEA-γGlu-C18 diacid, was synthesized using 2-chlorotrityl chloride resin as a solid support, and then was conjugated to the PTH1-34 variant to form PTH-Lys27-AGC. Reversed-phase chromatography confirmed a high final purity (>98%) of the target compound; in vitro bioactivity tests showed that PTH-1 receptor potency of PTH-Lys27-AGC was comparable to that of the native PTH1–34. A competitive human serum albumin binding test demonstrated a high albumin affinity of PTH-Lys27-AGC in comparison to PTH1–34. In summary, we developed a novel PTH1–34 analog, PTH-Lys27-AGC, which may be a long-acting agent for osteoporosis treatment in the future.

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Study on the interaction of ertugliflozin with human serum albumin in vitro by multispectroscopic methods, molecular docking, and molecular dynamics simulation

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy ◽

10.1016/j.saa.2019.04.047 ◽

2019 ◽

Vol 219 ◽

pp. 83-90 ◽

Cited By ~ 14

Author(s):

Wenjing Wang ◽

Na Gan ◽

Qiaomei Sun ◽

Di Wu ◽

Ruixue Gan ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Dynamics Simulation

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Nof2206Probing the interaction of memantine, an important Alzheimer's drug, with human serum albumin: In silico and In vitro approach

Journal of Molecular Liquids ◽

10.1016/j.molliq.2021.116888 ◽

2021 ◽

pp. 116888

Author(s):

Fahad A. Alhumaydhi ◽

Mohammad Abdullah Aljasir ◽

Abdullah S.M. Aljohani ◽

Suliman A. Alsagaby ◽

Ameen S.S. Alwashmi ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

In Silico

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Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin

Pharmaceuticals ◽

10.3390/ph14010022 ◽

2020 ◽

Vol 14 (1) ◽

pp. 22

Author(s):

Kenji Tsukigawa ◽

Shuhei Imoto ◽

Keishi Yamasaki ◽

Koji Nishi ◽

Toshihiko Tsutsumi ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Coupling Reaction ◽

Synthetic Polymer ◽

Ph Sensitive ◽

Acidic Ph ◽

Polymer Conjugate ◽

Acidic Conditions

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.

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The in Vitro Anti-HIV Efficacy of Negatively Charged Human Serum Albumin Is Antagonized by Heparin

AIDS Research and Human Retroviruses ◽

10.1089/aid.1997.13.677 ◽

1997 ◽

Vol 13 (8) ◽

pp. 677-683 ◽

Cited By ~ 3

Author(s):

P.J. SWART ◽

C.S. SUN ◽

M.E. KUIPERS ◽

C. ASUNCION ◽

S. JOSEPHS ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Anti Hiv

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Kinetic study of the photochemical changes of (ZZ)-bilirubin IX α bound to human serum albumin. Demonstration of (EZ)-bilirubin IX α as an intermediate in photochemical changes from (ZZ)-bilirubin IX α to (EZ)-cyclobilirubin IX α

Biochemical Journal ◽

10.1042/bj2260251 ◽

1985 ◽

Vol 226 (1) ◽

pp. 251-258 ◽

Cited By ~ 25

Author(s):

S Itoh ◽

S Onishi

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Kinetic Study ◽

Human Serum ◽

Photochemical Reaction ◽

Relative Rate ◽

Significant Preference ◽

Geometrical Isomers ◽

Relative Rate Constants

The present study was performed to elucidate why the photochemical reaction of (ZZ)-bilirubin bound to human serum albumin is singularly selective, and only one of the two (EZ)- and (ZE)-bilirubins, the (ZE)-isomer, is produced. In a kinetic study of the photochemical reaction in vitro, the sum of the relative rate constants of photochemical transformation of (EZ)-bilirubin into both (EZ)-cyclobilirubin and (ZZ)-bilirubin, with a significant preference for the former, was proved to be considerably larger than that of the transformation of (ZZ)-bilirubin into (EZ)-bilirubin. Therefore only one of the geometrical isomers, namely (ZE)-bilirubin, is apparently formed. It was concluded that (EZ)-bilirubin photochemically undergoes (EZ)-cyclization, i.e. structural photoisomerization, while bound to its high-affinity site on human serum albumin, and is an intermediate in the transformation of (ZZ)-bilirubin into (EZ)-cyclobilirubin.

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