Santángel worked as escribano de ración[1] to King Ferdinand II and Queen Isabella I of Spain which left him in charge of the Royal finance.

[2] In his professional life, in 1453, King John II of Aragon allowed Santángel to dedicate himself to the importation of cereals to Valencia, a product that fetched high prices during times of scarcity.

Isabella was still not convinced, and Columbus left the meeting upset, confiding in Santángel that he planned to seek financial funding from France or England—whichever nation agreed first.

This is how his son and biographer, Ferdinand Columbus, described the meeting: By the time January of 1492 had already begun, on the same day the Admiral departed from Santa Fe, much to the displeasure of many, including Luis de Santángel, whom we have previously mentioned, he, longing for a remedy, presented himself before the Queen.

With words inspired by his desire to persuade her, and at the same time to admonish her, he said that he was greatly amazed to see that, although Her Highness had always been prompt in spirit for every grave and important matter, she now lacked the same resolve to undertake another endeavor in which little was risked, yet from which so much service to God and the exaltation of His Church could result —not to mention the immense increase and glory it could bring to her kingdoms and states.

[7] Despite this protection and high status, Santángel was believed to have wanted to help Jews escape their persecution by funding Columbus's journey, which would potentially offer a safer place for them to reside.

[4] The descendant of Luis Santangel, Antonio de La Cadena Maluenda, born around 1490 and his sister Catalina settled 1525 in New Spain (Mexico) as the treasurer.

In April 2010, author Mitchell James Kaplan published a book titled By Fire, By Water[8] that explored a fictitious retelling of Luis de Santángel's life during the 15th century.

The novel, while not necessarily accurate, incorporated prominent events and situations such as Santángel's position in the Royal court, the Spanish Inquisition, and Columbus's journey.