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Article

Isolation and Identification of a Urinary Biomarker for Lung Cancer: 27-Nor-5β-Cholestane-3α,7α,12α,24R,25S Pentol Glucuronide and Its Deuterated Analog

1
Chemistry and Chemical Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, USA
2
AstraZeneca, 1 MedImmune Way, Gaithersburg, MD 20878, USA
3
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(12), 2781; https://doi.org/10.3390/molecules29122781
Submission received: 6 May 2024 / Revised: 1 June 2024 / Accepted: 3 June 2024 / Published: 11 June 2024
(This article belongs to the Section Organic Chemistry)

Abstract

An untargeted metabolomic study identified four potential lung cancer diagnostic biomarkers in human urine. One of the potential biomarkers was an unidentified feature possessing a m/z value of 561+. “561+” was isolated from human urine and tentatively identified as 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol glucuronide with unknown C24,25 stereochemistry using 1H NMR and mass spectrometry. In a prior report, the C24,25 stereochemistry of the aglycone, 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol, was found to be 24S,25R through GC analysis of the acetonide-TMS derivative. An authentic sample was prepared and found not to have the same stereochemistry as ”561+”. To identify the C24,25 stereochemistry, four C24,C25 diastereoisomeric alcohols of 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol were prepared from chiral amino acids. Using an LCMS method, the C24,C25 stereochemistry of the “561+” aglycone was determined to be 24R,25S. With the correct aglycone in hand, it was coupled with glucuronic acid to complete the first reported synthesis of 27-nor-5β-cholestane-3α,7α,12α,24R,25S pentol glucuronide. Deuterium labeled 27-nor-5β-cholestane-3α,7α,12α,24R,25S pentol was also synthesized for use as an internal standard for MS quantitation.
Keywords: lung cancer; chiral synthesis; biomarkers; 27-nor-5β-cholestane-3α,7α,12α,24,25-pentol; bile alcohol lung cancer; chiral synthesis; biomarkers; 27-nor-5β-cholestane-3α,7α,12α,24,25-pentol; bile alcohol

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MDPI and ACS Style

Blackman, B.; Raju, N.; Mushti, C.; Lane, K.; Patel, D.; Harris, C.; Swenson, R.E. Isolation and Identification of a Urinary Biomarker for Lung Cancer: 27-Nor-5β-Cholestane-3α,7α,12α,24R,25S Pentol Glucuronide and Its Deuterated Analog. Molecules 2024, 29, 2781. https://doi.org/10.3390/molecules29122781

AMA Style

Blackman B, Raju N, Mushti C, Lane K, Patel D, Harris C, Swenson RE. Isolation and Identification of a Urinary Biomarker for Lung Cancer: 27-Nor-5β-Cholestane-3α,7α,12α,24R,25S Pentol Glucuronide and Its Deuterated Analog. Molecules. 2024; 29(12):2781. https://doi.org/10.3390/molecules29122781

Chicago/Turabian Style

Blackman, Burchelle, Natarajan Raju, Chandrasekhar Mushti, Kelly Lane, Daxeshkumar Patel, Curtis Harris, and Rolf E. Swenson. 2024. "Isolation and Identification of a Urinary Biomarker for Lung Cancer: 27-Nor-5β-Cholestane-3α,7α,12α,24R,25S Pentol Glucuronide and Its Deuterated Analog" Molecules 29, no. 12: 2781. https://doi.org/10.3390/molecules29122781

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